In silico interrogation of the miRNAome of infected hematopoietic cells to predict processes important for human cytomegalovirus latent infection.

Human cytomegalovirus (HCMV) latency in CD34+ progenitor cells is the outcome of a complex and continued interaction of virus and host that is initiated during very early stages of infection and reflects pro- and anti-viral activity. We hypothesized that a key event during early infection could involve changes to host miRNAs, allowing for rapid modulation of the host proteome. Here, we identify 72 significantly upregulated miRNAs and three that were downregulated by 6hpi of infection of CD34+ cells which were then subject to multiple in silico analyses to identify potential genes and pathways important for viral infection. The analyses focused on the upregulated miRNAs and were used to predict potential gene hubs or common mRNA targets of multiple miRNAs. Constitutive deletion of one target, the transcriptional regulator JDP2, resulted in a defect in latent infection of myeloid cells; interestingly, transient knockdown in differentiated dendritic cells resulted in increased viral lytic IE gene expression, arguing for subtle differences in the role of JDP2 during latency establishment and reactivation of HCMV. Finally, in silico predictions identified clusters of genes with related functions (such as calcium signaling, ubiquitination, and chromatin modification), suggesting potential importance in latency and reactivation. Consistent with this hypothesis, we demonstrate that viral IE gene expression is sensitive to calcium channel inhibition in reactivating dendritic cells. In conclusion, we demonstrate HCMV alters the miRNAome rapidly upon infection and that in silico interrogation of these changes reveals new insight into mechanisms controlling viral gene expression during HCMV latency and, intriguingly, reactivation.

Emergency Ultrasound Unveils Intermediate-High Risk Saddle Pulmonary Embolism with Extensive Bilateral Clot Burden, Masquerading as Micturition Syncope: A Case Report.

BACKGROUND: Isolated syncope as the manifestation of pulmonary embolism (PE) is a rare and diagnostically challenging presentation that often leads to delayed or missed diagnosis, increasing morbidity and mortality. In spite of emphasizing cardiovascular etiologies of syncope, current guidelines offer essentially no guidance in establishing a diagnostic workup for PE in these patients. By performing bedside echocardiography, emergency physicians can accurately identify concerning features suggestive of PE in patients with syncope. CASE REPORT: A 78-year-old man, receiving ertapenem via a peripherally inserted central catheter for treatment of extended spectrum ß-lactamase urinary tract infection, presented to the emergency department for isolated syncope with collapse while urinating. Arriving asymptomatic with normal vital signs and a benign physical examination, a presumptive diagnosis of micturition syncope was made. However, subtle vital sign changes on reassessment prompted performance of a point-of-care echocardiogram, which revealed signs of right heart strain. A computed tomography angiogram confirmed a saddle PE with extensive bilateral clot burden. Catheter-directed thrombectomy was performed via interventional radiology, with successful removal of pulmonary emboli. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pulmonary embolism presenting as isolated syncope represents a daunting diagnostic dilemma, as emergency physicians may not consider it, or anchor on more benign etiologies of syncope. Although lacking sufficient sensitivity to rule out PE, point-of-care echocardiography to evaluate for signs of right heart strain can quickly and effectively point toward the diagnosis, while also assessing for other emergent cardiovascular causes of syncope. Given the lack of evidence-based guidance concerning PE presenting as syncope, bedside echocardiography should be highly considered as a part of the emergency physician's diagnostic workup, especially in patients with abnormal vital signs.

Exploring motivations for participating in research among Australian women with advanced gynaecological cancer: a qualitative study.

PURPOSE: With global moves to increase research among those living with advanced cancer and legitimise consumers as part of cancer research, this article aims to build an understanding of women's motivations and reasons for participating in gynaecological cancer research. As a secondary aim, we considered the role of qualitative methods in enabling active involvement of consumers in research. METHODS: We applied thematic discursive analysis to 18 in-depth interviews with women diagnosed with advanced (stage III-IV) gynaecological cancer living in Australia. RESULTS: We found that women viewed research as a vehicle for change in two directions: improving the lives of future generations and improving education and awareness. Underpinning these two framings of research, women spoke about their own role and reasons for participating in this interview study. Women's stories were painted against a backdrop of social and medical silences around gynaecological cancer. It was from such silence that women chose to speak up and position themselves as participating in service for knowledge production. CONCLUSION: We learned that trust, reciprocity and relationships are central to women's decisions to participate in cancer research. Legitimising consumers in cancer research requires methods, methodologies and practices that pay careful attention to power, control and representation.

Evasion of a Human Cytomegalovirus Entry Inhibitor with Potent Cysteine Reactivity Is Concomitant with the Utilization of a Heparan Sulfate Proteoglycan-Independent Route of Entry.

The dependence of viruses on the host cell to complete their replicative cycle renders cellular functions potential targets for novel antivirals. We screened a panel of broadly acting cellular ion channel inhibitors for activity against human cytomegalovirus (HCMV) and identified the voltage-gated chloride ion channel inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) as a potent inhibitor of HCMV replication. Time-of-addition studies demonstrated that DIDS inhibited entry via direct interaction with the virion that impeded binding to the plasma membrane. Synthesis and analysis of pharmacological variants of DIDS suggested that intrinsic cysteine, and not lysine, reactivity was important for activity against HCMV. Although sequencing of DIDS-resistant HCMV revealed enrichment of a mutation within UL100 (encoding glycoprotein M) and a specific truncation of glycoprotein RL13, these did not explain the DIDS resistance phenotype. Specifically, only the introduction of the RL13 mutant partially phenocopied the DIDS resistance phenotype. Serendipitously, the entry of DIDS-resistant HCMV also became independent of heparan sulfate proteoglycans (HSPGs), suggesting that evasion of DIDS lowered dependence on an initial interaction with HSPGs. Intriguingly, the DIDS-resistant virus demonstrated increased sensitivity to antibody neutralization, which mapped, in part, to the presence of the gM mutation. Taken together the data characterize the antiviral activity of a novel HCMV inhibitor that drives HCMV infection to occur independently of HSPGs and the generation of increased sensitivity to humoral immunity. The data also demonstrate that compounds with cysteine reactivity have the potential to act as antiviral compounds against HCMV via direct engagement of virions.IMPORTANCE Human cytomegalovirus (HCMV) is major pathogen of nonimmunocompetent individuals that remains in need of new therapeutic options. Here, we identify a potent antiviral compound (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid [DIDS]), its mechanism of action, and the chemical properties required for its activity. In doing so, the data argue that cysteine-reactive compounds could have the capacity to be developed for anti-HCMV activity. Importantly, the data show that entry of DIDS-resistant virus became independent of heparan sulfate proteoglycans (HSPGs) but, concomitantly, became more sensitive to neutralizing antibody responses. This serendipitous observation suggests that retention of an interaction with HSPGs during the entry process in vivo may be evolutionarily advantageous through better evasion of humoral responses directed against HCMV virions.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Get Healthy after Breast Cancer - examining the feasibility, acceptability and outcomes of referring breast cancer survivors to a general population telephone-delivered program targeting physical activity, healthy diet and weight loss.

PURPOSE: This pilot study assessed the feasibility, acceptability and outcomes of referring breast cancer survivors to the 'Get Healthy Service' (GHS), a state health-funded 6-month telephone-delivered lifestyle program. METHODS: Pre-post study with eligible and consenting women following treatment for stages I-III breast cancer referred by nurses in a cancer treatment centre to the GHS. Feasibility was assessed via GHS uptake and completion; acceptability was assessed via patient satisfaction and nurse feedback. Changes in weight, physical activity, diet, quality of life (QoL) and fatigue from baseline to 6 months were examined. RESULTS: Fifty-three women (mean ± SD body mass index, 31.0 ± 5.5 kg/m2; age, 57.3 ± 10.0 years; 14.0 ± 7.1 months post-diagnosis; 43.4% born outside Australia, 49% high school or less education, 32.1% English as a second language) took up the GHS, with 62% completing the program. Almost all (92%) completers had high satisfaction ratings and breast nurses provided positive feedback. Findings from GHS completers (n = 33) show a statistically significant effect from baseline to 6 months for weight loss (mean ± SE; -2.4 ± 0.7 kg; p = 0.002) and total physical activity minutes per week (55 ± 18 min/week; p = 0.006). No significant changes in fruit or vegetable servings per day or takeaways and fast food frequency per week were observed. A significant improvement in mental QoL was observed (3.5 ± 1.6; p = 0.041), but not for physical QoL or fatigue. CONCLUSION: GHS referral appeared feasible, acceptable and effective for a diverse group of women following completion of treatment for breast cancer, yet more remains to be done to fully integrate GHS screening and referral into usual care.

Identifying a Superfluid Reynolds Number via Dynamical Similarity.

The Reynolds number provides a characterization of the transition to turbulent flow, with wide application in classical fluid dynamics. Identifying such a parameter in superfluid systems is challenging due to their fundamentally inviscid nature. Performing a systematic study of superfluid cylinder wakes in two dimensions, we observe dynamical similarity of the frequency of vortex shedding by a cylindrical obstacle. The universality of the turbulent wake dynamics is revealed by expressing shedding frequencies in terms of an appropriately defined superfluid Reynolds number, Re(s), that accounts for the breakdown of superfluid flow through quantum vortex shedding. For large obstacles, the dimensionless shedding frequency exhibits a universal form that is well-fitted by a classical empirical relation. In this regime the transition to turbulence occurs at Re(s)≈0.7, irrespective of obstacle width.

Effectiveness of lifestyle-based weight loss interventions for adults with type 2 diabetes: a systematic review and meta-analysis.

AIMS: To provide a systematic review and meta-analysis of recent evidence on the effectiveness of lifestyle-based weight loss interventions for adults with type 2 diabetes. METHODS: A search of the literature from January 2003 to July 2013 was conducted (PubMed, Embase, CINAHL and Web of Science). The studies considered eligible were randomized controlled trials evaluating weight loss interventions (diet and physical activity, with or without behavioural strategies) of ≥12 weeks duration, compared with usual care or another comparison intervention. Ten studies were included for review. Some heterogeneity was present in the sample, therefore, random-effects models were used to calculate pooled effects. RESULTS: Intervention duration ranged from 16 weeks to 9 years, with all but one delivered via individual or group face-to-face sessions. From six studies comparing lifestyle intervention with usual care the pooled effect on weight (n = 5795) was -3.33 kg [95% confidence interval (CI) -5.06, -1.60 kg], and on glycated haemoglobin (HbA1c; n = 5784) was -0.29% (95% CI -0.61, 0.03%), with both attenuated in sensitivity analyses. The pooled within-group effect on weight (n = 3063) from all 10 lifestyle intervention groups was -5.33 kg (95% CI -7.33, -3.34 kg), also attenuated in sensitivity analyses. None of the participant or intervention characteristics examined explained the heterogeneity. Only one study assessed whether intervention effects were maintained after the end of the intervention. CONCLUSIONS: Lifestyle-based weight loss intervention trials in type 2 diabetes achieve, on average, modest reductions in weight and HbA1c levels, but results were heavily influenced by one trial. Evidence-based approaches for improving the effectiveness of lifestyle-based interventions in type 2 diabetes are needed, along with future studies reporting on maintenance and cost-effectiveness.

Onsager-Kraichnan condensation in decaying two-dimensional quantum turbulence.

Despite the prominence of Onsager's point-vortex model as a statistical description of 2D classical turbulence, a first-principles development of the model for a realistic superfluid has remained an open problem. Here we develop a mapping of a system of quantum vortices described by the homogeneous 2D Gross-Pitaevskii equation (GPE) to the point-vortex model, enabling Monte Carlo sampling of the vortex microcanonical ensemble. We use this approach to survey the full range of vortex states in a 2D superfluid, from the vortex-dipole gas at positive temperature to negative-temperature states exhibiting both macroscopic vortex clustering and kinetic energy condensation, which we term an Onsager-Kraichnan condensate (OKC). Damped GPE simulations reveal that such OKC states can emerge dynamically, via aggregation of small-scale clusters into giant OKC clusters, as the end states of decaying 2D quantum turbulence in a compressible, finite-temperature superfluid. These statistical equilibrium states should be accessible in atomic Bose-Einstein condensate experiments.

Small molecule- and amino acid-induced aggregation of gold nanoparticles.

To understand which organic molecules are capable of binding to gold nanoparticles and/or inducing nanoparticle aggregation, we investigate the interaction of gold nanoparticles with small molecules and amino acids at variable pH. Dynamic Light Scattering (DLS) and ultraviolet-visible (UV-vis) spectra were measured on mixtures of colloidal gold with small molecules to track the progression of the aggregation of gold nanoparticles. We introduce the 522 to 435 nm UV-vis absorbance ratio as a sensitive method for the detection of colloidal gold aggregation, whereby we delineate the ability of thiol, amine, and carboxylic acid functional groups to bind to the surfaces of gold nanoparticles and investigate how combinations of these functional groups affect colloidal stability. We present models for mechanisms of aggregation of colloidal gold, including surface charge reduction and bridging linkers. For all molecules whose addition leads to the aggregation of gold nanoparticles, the aggregation kinetics were accelerated at acidic pH values. Colloidal gold is maintained only in the presence of anionic carboxyl groups, which are neutralized by protonation at lower pH. The overall reduced charge on the stabilizing carboxyl groups accounts for the accelerated aggregation at lower pH values.

Six-month outcomes from living well with diabetes: A randomized trial of a telephone-delivered weight loss and physical activity intervention to improve glycemic control.

BACKGROUND: Intensive lifestyle intervention trials in type 2 diabetes contribute evidence on what can be achieved under optimal conditions, but are less informative for translation in applied settings. PURPOSE: Living Well with Diabetes is a telephone-delivered weight loss intervention designed for real-world delivery. METHODS: This study is a randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151); 6-month primary outcomes of weight, physical activity, HbA1c; secondary diet outcomes; analysis was by adjusted generalized linear models. RESULTS: Relative to usual care, telephone counseling participants had small but significantly better weight loss [-1.12 % of initial body weight; 95 % confidence interval (CI) -1.92, -0.33 %]; physical activity [relative rate (RR) = 1.30; 95 % CI, 1.08, 1.57]; energy intake reduction (-0.63 MJ/day; 95 % CI, -1.01, -0.25); and diet quality (3.72 points; 95 % CI, 1.77, 5.68), with no intervention effect for HbA1c (RR = 0.99; 95 % CI, 0.96, 1.01). CONCLUSIONS: Results are discussed in light of challenges to intervention delivery.

Costoclavicular Brachial Plexus Block Facilitates Painless Upper Extremity Reduction: A Case Report.

Introduction: The costoclavicular brachial plexus block (CCBPB) has emerged as a more effective approach to regional anesthesia of the upper extremity. The costoclavicular space is the anterior portion of the superior thoracic aperture, located between the clavicle and first rib. The brachial plexus cords traverse this space clustered together in a superficial location lateral to the axillary artery and share a consistent topographical relationship to one another. By targeting the brachial plexus at this specific anatomical location, the CCBPB offers a powerful, single-shot, sensorimotor block of the upper extremity below the shoulder. We present a novel application of the CCBPB to facilitate emergency department (ED) analgesia and closed reduction of an upper extremity fracture. Case Report: A 25-year-old male presented to the ED with a traumatic Colles fracture sustained during a high-speed motor vehicle collision. Despite multimodal analgesia, the patient reported intractable severe pain with intolerance of radial manipulation. An ultrasound-guided CCBPB was performed to augment pain control and avoid procedural sedation, resulting in dense, surgical anesthesia of the upper extremity, and painless fracture reduction. Conclusion: Regional anesthesia is an effective component of multimodal pain management and another tool in the emergency physician's analgesic armamentarium. In acute orthopedic traumas necessitating emergent reduction, regional blocks serve as rescue pain control and can obviate the need for procedural sedation. In terms of targeted upper extremity analgesia, the CCBPB offers effective, single-shot, sensorimotor blockade below the shoulder, mitigating use of opioids and their deleterious side effects, while simultaneously avoiding incomplete blockade or phrenic nerve palsy associated with other approaches to brachial plexus blockade.

LSD1/KDM1A is essential for neural stem cell differentiation in mice.

The proper regulation of neural stem cell differentiation is required for the proper specification of the central nervous system. Here we investigated the function of the H3K4me1/2 demethylase LSD1/KDM1A during neural stem differentiation in mice. Conditional deletion of LSD1 in nestin- positive neural stem cells results in 100% perinatal lethality after birth with severe motor coordination deficits, retarded growth and defects in brain morphology. Despite these severe defects, motor neuron progenitors and the initial motor neuron population are specified normally and motor neurons with normal morphology can be cultured from these mice in vitro. However, motor neurons cultured from mice lacking LSD1 in neural stem cells continue to inappropriately maintain critical neural stem cell proteins. Taken together these results suggest that, as in other mouse stem cell populations, LSD1 is required to deactivate the stem cell program to enable normal neural stem cell differentiation. However, unlike in other mouse stem cell populations, the inappropriate maintenance of the stem cell program during neural stem cell differentiation may compromise neuronal function rather than neuronal specification.

The cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread.

Vaccination against human cytomegalovirus (CMV) infection remains high priority. A recombinant form of a protein essential for CMV entry, glycoprotein B (gB), demonstrated partial protection in a clinical trial (NCT00299260) when delivered with the MF59 adjuvant. Although the antibody titre against gB correlated with protection poor neutralising responses against the 5 known antigenic domains (AD) of gB were evident. Here, we show that vaccination of CMV seronegative patients induces an antibody response against a region of gB we term AD-6. Responses to the polypeptide AD-6 are detected in >70% of vaccine recipients yet in <5% of naturally infected people. An AD-6 antibody binds to gB and to infected cells but not the virion directly. Consistent with this, the AD-6 antibody is non-neutralising but, instead, prevents cell-cell spread of CMV in vitro. The discovery of AD-6 responses has the potential to explain part of the protection mediated by gB vaccines against CMV following transplantation.

Evaluating the competing risks of HIV acquisition and maternal mortality in Africa: a decision analysis.

OBJECTIVE: To model the risk of HIV acquisition and maternal mortality for women in four African countries in the light of previous data on risk of HIV acquisition and hormonal contraceptive use. DESIGN: Decision analysis. SETTING: Chad, Kenya, South Africa and Uganda. POPULATION: Women of reproductive age, at risk of HIV, who do not desire pregnancy. METHODS: A decision analysis model was built to compare the consequences of removing progestin injectables from use, assuming an increased risk of HIV acquisition. Three scenarios were considered in four African countries: replacement of progestin injectables with no method, with combined oral contraceptives (COC) or with an intrauterine device (IUD). Health outcomes measured include: life-years, maternal mortality, HIV acquisition and unsafe abortion. Sensitivity analysis, including Monte Carlo simulation, was performed around all variables. MAIN OUTCOME MEASURES: HIV acquisition, maternal mortality and life-years. RESULTS: If progestin injectables are removed from use, without a minimum of 70-100% of women switching to an IUD or COCs, up to nine additional maternal deaths will occur for every case of HIV averted. Sensitivity analysis demonstrated that this finding persisted across a broad range of variables. CONCLUSIONS: Contraception is critical to preserving life for women in Africa. In the absence of clear evidence regarding hormonal contraception and HIV acquisition, policy decisions must not overlook the very real risk of maternal mortality.

Health-related fitness and academic achievement in middle school students.

AIM: The aim of the present study was to determine the association between health-related fitness (HRF) and academic achievement in middle school youth. METHODS: Subjects were 312 middle school students. HRF was assessed using the FITNESSGRAM test battery. Students were grouped by the number of fitness tests in which they performed within the Healthy Fitness Zone, ranging from <1 test (lowest fitness) to all 5 tests (highest fitness). Academic achievement was assessed using grades (A - F) from four core classes, which were converted to interval data (A=5, F=1) and summed over the academic year and a standardized test (percentile). Maturity offset was calculated to control for the possible effect of maturity status on the association between HRF and academic achievement. Differences in academic achievement among HRF groups were determined using ANOVA. RESULTS: Grades and standardized test percentiles were higher in HRF group 5 (P<0.01) compared to HRF groups <2, 3, and 4. Cardiorespiratory endurance and muscular strength and endurance were the HRF components most strongly associated with academic achievement. CONCLUSION: HRF was related to academic achievement in youth. Students with the highest fitness level performed better on standardized tests and students with the lowest fitness level performed lower in class grades.

Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases.

Dendritic cells (DCs) are bone marrow-derived leukocytes that function as potent antigen presenting cells capable of initiating T cell-dependent responses from quiescent lymphocytes. DC pulsed with tumor-associated antigen (TAA) peptide or protein have recently been demonstrated to elicit antigen-specific protective antitumor immunity in a number of murine models. Transduction of DCs with TAA genes may allow stable, prolonged antigen expression as well as the potential for presentation of multiple, or unidentified, epitopes in association with major histocompatibility complex class I and/or class II molecules. To evaluate the potential efficacy of retrovirally transduced DCs, bone marrow cells harvested from BALB/c mice were transduced with either a model antigen gene encoding beta-galactosidase (beta-gal) or a control gene encoding rat HER-2/neu (Neu) by coculture with irradiated ecotropic retroviral producer lines. Bone marrow cells were differentiated into DC in vitro using granulocyte/macrophage colony-stimulating factor and interleukin-4. After 7 d in culture, cells were 45-78% double positive for DC phenotypic cell surface markers by FACS(R) analysis, and DC transduced with beta-gal were 41-72% positive for beta-gal expression by X-gal staining. In addition, coculture of beta-gal transduced DC with a beta-gal-specific T cell line (CTLx) resulted in the production of large amounts of interferon-gamma, demonstrating that transduced DCs could process and present endogenously expressed beta-gal. DC transduced with beta-gal and control rat HER-2/neu were then used to treat 3-d lung metastases in mice bearing an experimental murine tumor CT26.CL25, expressing the model antigen, beta-gal. Treatment with beta-gal-transduced DC significantly reduced the number of pulmonary metastatic nodules compared with treatment with Hank's balanced salt solution or DCs transduced with rat HER-2/neu. In addition, immunization with beta-gal-transduced DCs resulted in the generation of antigen-specific cytotoxic T lymphocytes (CTLs), which were significantly more reactive against relevant tumor targets than CTLs generated from mice immunized with DCs pulsed with the Ld-restricted beta-gal peptide. The results observed in this rapidly lethal tumor model suggest that DCs transduced with TAA may be a useful treatment modality in tumor immunotherapy.

Gender differences in prevalence of the metabolic syndrome in Gulf Cooperation Council Countries: a systematic review.

AIMS: To systematically review studies documenting the prevalence of the metabolic syndrome among men and women in Member States of the Gulf Cooperative Council (GCC; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates)-countries in which obesity, Type 2 diabetes and related metabolic and cardiovascular diseases are highly prevalent. METHODS: A search was conducted on PubMed and CINAHL using the term 'metabolic syndrome' and the country name of each GCC Member State. The search was limited to studies published in the English language. The metabolic syndrome was defined according to the Third Adult Treatment Panel (ATPIII) of the National Cholesterol Education Program (NCEP) and/or International Diabetes Federation (IDF) definitions. The methodological quality of each study was evaluated based on four criteria: a national-level population sample; equal gender representation; robustness of the sample size; an explicit sampling methodology. RESULTS: PubMed, CINAHL and reference list searches identified nine relevant studies. Only four were considered high quality and found that, for men, the prevalence of the metabolic syndrome ranged from 20.7% to 37.2% (ATPIII definition) and from 29.6% to 36.2% (IDF definition); and, for women, from 32.1% to 42.7% (ATPIII definition) and from 36.1% to 45.9% (IDF definition). CONCLUSIONS: Overall, the prevalence of the metabolic syndrome in the GCC states is some 10-15% higher than in most developed countries, with generally higher prevalence rates for women. Preventive strategies will require identifying socio-demographic and environmental correlates (particularly those influencing women) and addressing modifiable risk behaviours, including lack of physical activity, prolonged sitting time and dietary intake.

Communication of adenomyosis with the endometrial cavity: visualization with saline contrast sonohysterography.

We report four cases of a finding of communication between the endometrial cavity and adenomyotic lesions observed during saline contrast sonohysterography. In each case there was a saline-filled defect extending from the endometrial cavity into the myometrium in the region of previously suspected adenomyosis. We believe this finding represents the sonohysterographic correlate of endometrium invading the myometrium, as has been described histologically.

The human selenoproteome: recent insights into functions and regulation.

Selenium (Se) is a nutritional trace mineral essential for various aspects of human health that exerts its effects mainly through its incorporation into selenoproteins as the amino acid, selenocysteine. Twenty-five selenoprotein genes have been identified in humans and several selenoproteins are broadly classified as antioxidant enzymes. As progress is made on characterizing the individual members of this protein family, however, it is becoming clear that their properties and functions are quite diverse. This review summarizes recent insights into properties of individual selenoproteins such as tissue distribution, subcellular localization, and regulation of expression. Also discussed are potential roles the different selenoproteins play in human health and disease.