Dark-Blood Delayed Enhancement Cardiac Magnetic Resonance of Myocardial Infarction

Objectives

This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal.

Controlling the size of nanoscale toroidal DNA condensates with static curvature and ionic strength

The process of DNA condensation into nanometer-scale particles has direct relevance to several fields, including cell biology, virology, and gene delivery for therapeutic purposes. DNA condensation has also attracted the attention of polymer physicists, as the collapse of DNA molecules from solution into well defined particles represents an exquisite example of a polymer phase transition. Here we present a quantitative study of DNA toroids formed by condensation of 3 kb DNA with hexammine cobalt (III). The presence or absence of static loops within this DNA molecule demonstrates the effect of nucleation loop size on toroid dimensions and that nucleation is principally decoupled from toroid growth. A comparison of DNA condensates formed at low ionic strength with those formed in the presence of additional salts (NaCl or MgCl2) shows that toroid thickness is a salt-dependant phenomenon. Together, these results have allowed the development of models for DNA toroid formation in which the size of the nucleation loop directly influences the diameter of the fully formed toroid, whereas solution conditions govern toroid thickness. The data presented illustrate the potential that exists for controlling DNA toroid dimensions. Furthermore, this study provides a set of data that should prove useful as a test for theoretical models of DNA condensation.     

Adenosine receptors in regulation of dendritic cell differentiation and function

Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes and mouse peritoneal macrophages and hematopoietic progenitor cells (HPCs) into myeloid DCs. Stimulation of adenosine receptors skews DC differentiation toward a distinct cell population characterized by expression of both DC and monocyte/macrophage cell surface markers. Pharmacologic analysis and experiments with cells from A(2B) adenosine receptor knockout mice identified A(2B) receptor as the mediator of adenosine effects on DCs. Unlike normal myeloid DCs, adenosine-differentiated DCs have impaired allostimulatory activity and express high levels of angiogenic, pro-inflammatory, immune suppressor, and tolerogenic factors, including VEGF, IL-8, IL-6, IL-10, COX-2, TGF-beta, and IDO. They promoted tumor growth if injected into tumors implanted in mice. Using adenosine desaminase knockout animals, we showed that DCs with proangiogenic phenotype are highly abundant under conditions associated with elevated levels of extracellular adenosine in vivo. Adenosine signaling through A(2B) receptor is an important factor of aberrant DC differentiation and generation of tolerogenic, angiogenic, and proinflammatory cells.     

Helicobacter pylori Infection in Infants and Toddlers in South America: Concordance between [13C]Urea Breath Test and Monoclonal H. pylori Stool Antigen Test

Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [¹³C]urea breath test ([¹³C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian (n = 415) and Peruvian (n = 908) infants. [¹³C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori-positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated (r = 0.62; P < 0.001). The positivity of the tests was higher (P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil (P = 0.02), whereas in Peru it decreased with increasing age (P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [¹³C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.     

Diagnostic and Prognostic Value of Low Density Lipoprotein-Containing Circulating Immune Complexes in Atherosclerosis

Recently, it has been shown that increased level of LDL-containing circulating immune complexes (LDL-CIC) possess high diagnostic significance in clinically manifested atherosclerosis, but little is known about its diagnostic and prognostic significance in early atherosclerosis. Two-years prospective study was performed in 98 asymptomatic men aged 40–74. The rate of atherosclerosis progression was estimated by high-resolution B-mode ultrasonography as the increase in intima-media thickness (IMT) of common carotid arteries. The patients with elevated baseline levels of LDL-CIC were characterized by significantly higher levels of total and LDL cholesterol as well as significantly increased mean IMT of common carotid arteries. Among all baseline lipid parameters, only LDL-CIC and LDL cholesterol were contingent with the extent of early carotid atherosclerosis (p?=?0.042 and p?=?0.049, respectively) and had the highest levels of relative risk and odds ratio. During the follow up, significant IMT increase was registered in 53.1 % (n?=?52) patients, IMT significant reduction was observed in 21.4 % (n?=?21) patients. The increased levels of LDL-CIC, total serum cholesterol and LDL cholesterol had similar prognostic significance with the respect of atherosclerosis progression. The normal level of LDL-CIC (below than 16.0 μg/ml) was the only lipid parameter that predicted the absence of carotid atherosclerosis progression for two following years at prognostic value of 78.3 %. The results of the study allow assuming that LDL-CIC level may be employed not only as a marker of early atherosclerosis, but also has a sufficient prognostic value for clinical implications.     

Assessing the predictive ability of the Suicide Crisis Inventory for near‐term suicidal behavior using machine learning approaches

ObjectiveThis study explores the prediction of near‐term suicidal behavior using machine learning (ML) analyses of the Suicide Crisis Inventory (SCI), which measures the Suicide Crisis Syndrome, a presuicidal mental state.MethodsSCI data were collected from high‐risk psychiatric inpatients (N = 591) grouped based on their short‐term suicidal behavior, that is, those who attempted suicide between intake and 1‐month follow‐up dates (N = 20) and those who did not (N = 571). Data were analyzed using three predictive algorithms (logistic regression, random forest, and gradient boosting) and three sampling approaches (split sample, Synthetic minority oversampling technique, and enhanced bootstrap).ResultsThe enhanced bootstrap approach considerably outperformed the other sampling approaches, with random forest (98.0% precision; 33.9% recall; 71.0% Area under the precision‐recall curve [AUPRC]; and 87.8% Area under the receiver operating characteristic [AUROC]) and gradient boosting (94.0% precision; 48.9% recall; 70.5% AUPRC; and 89.4% AUROC) algorithms performing best in predicting positive cases of near‐term suicidal behavior using this dataset.ConclusionsML can be useful in analyzing data from psychometric scales, such as the SCI, and for predicting near‐term suicidal behavior. However, in cases such as the current analysis where the data are highly imbalanced, the optimal method of measuring performance must be carefully considered and selected.     

Oncoplastic Surgery in Breast-Conserving Treatment: Patient Profile and Impact on Quality of Life

BackgroundBreast-conserving treatment (BCT) provides better quality of life (QL) than mastectomy without reconstruction. Oncoplastic surgery (OS) encompasses a series of surgical techniques, increasing the indications for BCT, but few studies have evaluated the impact on QL in patients who undergo BCT with OS.Materials and MethodsA prospective, cross-sectional study was conducted in women who underwent BCT. We evaluated the characteristics of patients who underwent BCT with and without OS and the associated QL. QL was assessed through the EORTC QLQ-30, EORTC QLQ-BR23, and Breast Cancer Treatment Outcome Scale (BCTOS) questionnaires.ResultsA total of 300 patients underwent BCT, 72 underwent breast OS, and 37 underwent bilateral surgery. Patients who underwent OS were younger (p = 0.004), had a higher level of education (p = 0.01), had a smaller time interval since the end of treatment (p = 0.02), had tumours with greater dimensions (p = 0.003), and were more likely to receive neoadjuvant chemotherapy (p = 0.05). Based on the QL questionnaires, no difference was observed between the groups. Breast symmetry was not associated with high patient satisfaction (p = 0.55).ConclusionDespite the fact that OS was performed in patients with worse tumour conditions and in more demanding patients, OS allowed similar cosmetic results to classical BCT.     

Anterior vs Posterior Hippocampal Subfields in an Extended Psychosis Phenotype of Multidimensional Schizotypy in a Nonclinical Sample

Numerous studies have implicated involvement of the hippocampus in the etiology and expression of schizophrenia-spectrum psychopathology, and reduced hippocampal volume is one of the most robust brain abnormalities reported in schizophrenia. Recent studies indicate that early stages of schizophrenia are specifically characterized by reductions in anterior hippocampal volume; however, studies have not examined hippocampal volume reductions in subclinical schizotypy. The present study was the first to examine the associations of positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults, phenotyped using the Multidimensional Schizotypy Scale (MSS). Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres. We demonstrate differential spatial effects across anterior vs posterior hippocampus segments across different dimensions of the schizotypy risk phenotype. The interaction of negative and disorganized schizotypy robustly predicted left hemisphere volumetric reductions for the anterior and total hippocampus, and anterior CA and DG, and the largest reductions were seen in participants high in negative and disorganized schizotypy. These findings extend previous early psychosis studies and together with behavioral studies of hippocampal-related memory impairments provide the basis for a dimensional neurobiological hippocampal model of schizophrenia risk. Subtle hippocampal subfield volume reductions may be prevalent prior to the onset of detectable prodromal clinical symptoms of psychosis and play a role in the etiology and development of such conditions.     

Estimating global and regional morbidity from acute bacterial meningitis in children: assessment of the evidence

Aim

To estimate global morbidity from acute bacterial meningitis in children.

Methods

We conducted a systematic review of the PubMed and Scopus databases to identify both community-based and hospital registry-based studies that could be useful in estimation of the global morbidity from bacterial meningitis in children. We were primarily interested in the availability and quality of the information on incidence rates and case-fatality rates. We assessed the impact of the year of study, study design, study setting, the duration of study, and sample size on reported incidence values, and also any association between incidence and case-fatality rate. We also categorized the studies by 6 World Health Organization regions and analyzed the plausibility of estimates derived from the current evidence using median and inter-quartile range of the available reports in each region.

Results

We found 71 studies that met the inclusion criteria. The only two significant associations between the reported incidence and studied covariates were the negative correlation between the incidence and sample size (P < 0.001) and positive correlation between incidence and case-fatality rate (P < 0.001). The median incidence per 100 000 child-years was highest in the African region – 143.6 (interquartile range [IQR] 115.6-174.6), followed by Western Pacific region with 42.9 (12.4-83.4), the Eastern Mediterranean region with 34.3 (9.9-42.0), South East Asia with 26.8 (21.0-60.3), Europe with 20.8 (16.2-29.7), and American region with 16.6 (10.3-33.7). The median case-fatality rate was also highest in the African region (31.3%). Globally, the median incidence for all 71 studies was 34.0 (16.0-88.0) per 100 000 child-years, with a median case-fatality rate of 14.4% (5.3%-26.2%).

Conclusions

Our study showed that there was now sufficient evidence to generate improved and internally consistent estimates of the global burden of acute bacterial meningitis in children. Although some of our region-specific estimates are very uncertain due to scarcity of data from the corresponding regions, the estimates of morbidity and case-fatality from childhood bacterial meningitis derived from this study are consistent with mortality estimates derived from multi-cause mortality studies. Both lines of evidence imply that bacterial meningitis is a cause of 2% of all child deaths.Meningitis is an infectious disease affecting the brain membrane and spinal cord (1). Globally, bacterial meningitis is the most severe type of meningitis, mainly caused by a triad of species Neisseria meningitidis, Streptocccus pneumonia, and Haemophilus influenzae (2). While viral meningitis is usually a self-limiting disease with good prognosis, bacterial meningitis is potentially fatal, requiring urgent medical assistance and management with antibiotics treatment (3). Various estimates of the burden of bacterial meningitis have been proposed to date, but they have mainly focused on mortality (4), long-term sequels (5), or etiology-specific morbidity and mortality (6-8).Interestingly, there have been no comprehensive attempts to estimate the overall global burden of bacterial meningitis in children. This is not surprising, because such attempt would face almost insurmountable methodological challenges. First, there is a problem with case definition of “bacterial meningitis” (9). In low resource settings, where the problem is most common, many children may present with “purulent meningitis,” whose cause is highly likely bacterial, but laboratory capacity may not be sufficient to isolate the causal agent and confirm the diagnosis. This leads to a discrepancy between morbidity burden estimates based on “all purulent meningitis” and “laboratory confirmed meningitis” – the latter always being lower than the former, but to a different extent in different contexts (10). The second large methodological obstacle is the problem of “meningitis belt.” The meningitis belt is the band of countries extending from Senegal to Ethiopia, characterized by semi-arid climate, dry seasons, and dusty winds, with seasonal outbreaks of meningococcal meningitis being recorded since the beginning of the 20th century (11). The problem with these epidemics is that they can last for several years and dramatically change the importance of meningococcus in comparison to the other two bacterial agents (S. pneumoniae and H. influenzae) both regionally and globally (11). This makes it difficult to express the “burden of disease” for any given year, because it will be very different in intra-epidemic and inter-epidemic years. Moreover, the extent of vaccine coverage against N. meningitidis, S. pneumoniae and H. influenzae is changing the burden rapidly and rather dramatically in many places, rendering the scarce evidence from before the period of vaccination rather useless and indicates a need of revision (12). Finally, the emergence of HIV/AIDS pandemic led to a substantial number of infected children, whose resistance to other infections is impaired and they present a specific category of population in which the rates of incidence and case-fatality rates may be very different from those in other children (13).It is apparent that meningitis continues to contribute significantly to global mortality and morbidity, but the impact of the efforts to control it is difficult to estimate given that we do not have comprehensive estimates of global morbidity patterns. Understanding the global morbidity from bacterial meningitis would be useful because it would also help to validate the existing mortality estimates through application of appropriate case-fatality rates. The purpose of the present study is to provide a comprehensive assessment of the evidence that is available for estimating the global morbidity from acute bacterial meningitis in children globally. We will also propose initial, robust estimates of the burden, with suggestions on the possible ways to address the methodological challenges in future studies.     

The strength of primary care in Europe: an international comparative study

Background

A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking.

Aim

Evaluation of strength of primary care in Europe.

Design and setting

International comparative cross-sectional study performed in 2009–2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey.

Method

Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts’ consultations.

Results

Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries.

Conclusion

Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.