Positive and negative evaluation of caregiving among three different types of informal care relationships

Based on the caregiver stress model, we examined how care demands, caregiver motivation, coping style and external support are associated with positive evaluation and caregiver burden among spousal, adult child and other types of care relations. Data from a sample of Dutch informal caregivers of 1,685 older persons (55 and older) were analyzed employing multivariate linear regression analyses for each of the care relationship types. Spouses (N = 206) report high positive evaluation and high burden, adult children (N = 1,093) report low positive evaluation, and other caregivers (N = 386) report high positive evaluation and a low burden. Multivariate linear regression analyses showed that motives and external support were important for positive evaluation but the impact varied among types of caregivers, whereas care demands and not asking for help were associated with burden for all types. Only among 'other' caregiver relationships, positive evaluation was negatively associated with burden. It is concluded that results confirm the dual nature of caregiving among spouses and children. The care context and motivation of the different types of caregivers explain their differences in care evaluation. Various interventions for types of caregivers are discussed. © 2013 Springer-Verlag Berlin Heidelberg

Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection

Vaccination with J8-DT, a leading GAS vaccine candidate, results in protective immunity in mice. Analysis of immunologic correlates of protection indicated a role of J8-specific antibodies that were induced post-immunization. In the present study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved in J8-DT-mediated immunity. These approaches included the passive transfer of mouse or rabbit immune serum/antibodies in addition to selective depletion of T-cell subsets prior to bacterial challenge. Passive transfer of J8-DT antiserum/antibodies from mice and rabbits conferred significant resistance against challenge to mice. To exclude the possibility of involvement of other host immune factors, the studies were repeated in SCID mice, which highlighted the need for an ongoing immune response for long-lived protection. Depletion of CD4+ and CD8+ T-cell subsets confirmed that an active de novo immune response, involving CD4+ T-helper cells, is required for continued synthesis of antibodies resulting in protection against GAS infection. Taken together these results indicate an involvement of CD4+ T-cells in J8-DT-mediated protection possibly via an ability to maintain antibody levels. These results have considerable relevance to the development of a broad spectrum passive immunotherapy for GAS disease

Hemoglobin levels and anemia evaluation during pregnancy in the highlands of Tibet: a hospital-based study

<p>Abstract</p> <p>Background</p> <p>Anemia is regarded as a major risk factor for unfavorable pregnancy outcomes, but there have been no previous studies describing the pattern of hemoglobin concentration during pregnancy in Tibet and the relationship between altitude and Hb concentration in the pregnant women living in Tibet still has not been clearly established. The main objectives of this study were to study the hemoglobin levels and prevalence of anemia among pregnant women living in the highlands of Tibet and to evaluate potential associations of hemoglobin and anemia with women's characteristics.</p> <p>Methods</p> <p>The hospital-based study was conducted in 380 pregnant women. Their blood samples were tested and related sociodemographic information was collected. Multiple linear regression model and multiple logistic regression model were used to assess the association of pregnant women's characteristics with hemoglobin level and the occurrence of anemia. Centers for Disease Control (CDC), Dirren et al. and Dallman et al. methods were used to adjust the hemoglobin measurements based on altitude for estimating the prevalence of anemia.</p> <p>Results</p> <p>The mean hemoglobin concentration was 127.6 g/L (range: 55.0-190.0 g/L). Prevalence rate of anemia in this study was 70.0%, 77.9% and 41.3%, respectively for three altitude-correction methods for hemoglobin (CDC method, Dirren et al. method, and Dallman et al. method). Gestational age, ethnicity, residence and income were significantly associated with the hemoglobin concentration and prevalence of anemia in the study population. Specially, the hemoglobin concentration of pregnant women decreased with increase in gestational age.</p> <p>Conclusion</p> <p>The hemoglobin level was low and prevalence rate of anemia was high among pregnant women in Lhasa, Tibet. Gestational age, ethnicity, residence and income were found to be significantly associated with the hemoglobin level and the occurrence of anemia in the study population.</p

Ag85-focused T-cell immune response controls Mycobacterium avium chronic infection

CD4+ T cells are essential players for the control of mycobacterial infections. Several mycobacterial antigens have been identified for eliciting a relevant CD4+ T cell mediated-immune response, and numerous studies explored this issue in the context of Mycobacterium tuberculosis infection. Antigen 85 (Ag85), a highly conserved protein across Mycobacterium species, is secreted at the early phase of M. tuberculosis infection leading to the proliferation of Ag85-specific CD4+ T cells. However, in the context of Mycobacterium avium infection, little is known about the expression of this antigen and the elicited immune response. In the current work, we investigated if a T cell receptor (TCR) repertoire mostly, but not exclusively, directed at Ag85 is sufficient to mount a protective immune response against M. avium. We show that P25 mice, whose majority of T cells express a transgenic TCR specific for Ag85, control M. avium infection at the same level as wild type (WT) mice up to 20 weeks post-infection (wpi). During M. avium infection, Ag85 antigen is easily detected in the liver of 20 wpi mice by immunohistochemistry. In spite of the propensity of P25 CD4+ T cells to produce higher amounts of interferon-gamma (IFNγ) upon ex vivo stimulation, no differences in serum IFNγ levels are detected in P25 compared to WT mice, nor enhanced immunopathology is detected in P25 mice. These results indicate that a T cell response dominated by Ag85-specific T cells is appropriate to control M. avium infection with no signs of immunopathology.This work was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Fellowships from the Portuguese Foundation for Science and Technoloy (FCT) were attributed to BCR (SFRH/BD/80352/2011; QREN-POPH through the Fundo Social Europeu (FSE) and national funds from MEC] and to CN (SFRH/BPD/112001/2015; POPH through FSE and national funds from MCTES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The quality of research synthesis in surgery: the case of laparoscopic surgery for colorectal cancer

Peer reviewedPublisher PD

Technical efficiency of peripheral health units in Pujehun district of Sierra Leone: a DEA application

BACKGROUND: The Data Envelopment Analysis (DEA) method has been fruitfully used in many countries in Asia, Europe and North America to shed light on the efficiency of health facilities and programmes. There is, however, a dearth of such studies in countries in sub-Saharan Africa. Since hospitals and health centres are important instruments in the efforts to scale up pro-poor cost-effective interventions aimed at achieving the United Nations Millennium Development Goals, decision-makers need to ensure that these health facilities provide efficient services. The objective of this study was to measure the technical efficiency (TE) and scale efficiency (SE) of a sample of public peripheral health units (PHUs) in Sierra Leone. METHODS: This study applied the Data Envelopment Analysis approach to investigate the TE and SE among a sample of 37 PHUs in Sierra Leone. RESULTS: Twenty-two (59%) of the 37 health units analysed were found to be technically inefficient, with an average score of 63% (standard deviation = 18%). On the other hand, 24 (65%) health units were found to be scale inefficient, with an average scale efficiency score of 72% (standard deviation = 17%). CONCLUSION: It is concluded that with the existing high levels of pure technical and scale inefficiency, scaling up of interventions to achieve both global and regional targets such as the MDG and Abuja health targets becomes far-fetched. In a country with per capita expenditure on health of about US$7, and with only 30% of its population having access to health services, it is demonstrated that efficiency savings can significantly augment the government's initiatives to cater for the unmet health care needs of the population. Therefore, we strongly recommend that Sierra Leone and all other countries in the Region should institutionalise health facility efficiency monitoring at the Ministry of Health headquarter (MoH/HQ) and at each health district headquarter

Complexity of Bidirectional Transcription and Alternative Splicing at Human RCAN3 Locus

Human RCAN3 (regulator of calcineurin 3) belongs to the human RCAN gene family

Large-scale integration of cancer microarray data identifies a robust common cancer signature

<p>Abstract</p> <p>Background</p> <p>There is a continuing need to develop molecular diagnostic tools which complement histopathologic examination to increase the accuracy of cancer diagnosis. DNA microarrays provide a means for measuring gene expression signatures which can then be used as components of genomic-based diagnostic tests to determine the presence of cancer.</p> <p>Results</p> <p>In this study, we collect and integrate ~ 1500 microarray gene expression profiles from 26 published cancer data sets across 21 major human cancer types. We then apply a statistical method, referred to as the <it>T</it>op-<it>S</it>coring <it>P</it>air of <it>G</it>roups (TSPG) classifier, and a repeated random sampling strategy to the integrated training data sets and identify a common cancer signature consisting of 46 genes. These 46 genes are naturally divided into two distinct groups; those in one group are typically expressed less than those in the other group for cancer tissues. Given a new expression profile, the classifier discriminates cancer from normal tissues by ranking the expression values of the 46 genes in the cancer signature and comparing the average ranks of the two groups. This signature is then validated by applying this decision rule to independent test data.</p> <p>Conclusion</p> <p>By combining the TSPG method and repeated random sampling, a robust common cancer signature has been identified from large-scale microarray data integration. Upon further validation, this signature may be useful as a robust and objective diagnostic test for cancer.</p

TLR2 and Nod2 Mediate Resistance or Susceptibility to Fatal Intracellular Ehrlichia Infection in Murine Models of Ehrlichiosis

Our murine models of human monocytic ehrlichiosis (HME) have shown that severe and fatal ehrlichiosis is due to generation of pathogenic T cell responses causing immunopathology and multi-organ failure. However, the early events in the liver, the main site of infection, are not well understood. In this study, we examined the liver transcriptome during the course of lethal and nonlethal infections caused by Ixodes ovatus Ehrlichia and Ehrlichia muris, respectively. On day 3 post-infection (p.i.), although most host genes were down regulated in the two groups of infected mice compared to naïve counterparts, lethal infection induced significantly higher expression of caspase 1, caspase 4, nucleotide binding oligomerization domain-containing proteins (Nod1), tumor necrosis factor-alpha, interleukin 10, and CCL7 compared to nonlethal infection. On day 7 p.i., lethal infection induced highly significant upregulation of type-1 interferon, several inflammatory cytokines and chemokines, which was associated with increased expression levels of Toll-like receptor-2 (TLR2), Nod2, MyD88, nuclear factor-kappa B (NF-kB), Caspase 4, NLRP1, NLRP12, Pycard, and IL-1β, suggesting enhanced TLR signals and inflammasomes activation. We next evaluated the participation of TLR2 and Nod2 in the host response during lethal Ehrlichia infection. Although lack of TLR2 impaired bacterial elimination and increased tissue necrosis, Nod2 deficiency attenuated pathology and enhanced bacterial clearance, which correlated with increased interferon-γ and interleukin-10 levels and a decreased frequency of pathogenic CD8+ T cells in response to lethal infection. Thus, these data indicate that Nod2, but not TLR2, contributes to susceptibility to severe Ehrlichia-induced shock. Together, our studies provide, for the first time, insight into the diversity of host factors and novel molecular pathogenic mechanisms that may contribute to severe HME. © 2013 Chattoraj et al

Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture

Cardiac arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov) model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study