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Evaluation of immunomodulation by Lactobacillus casei Shirota: immune function, autoimmunity and gene expression.

Lactic acid bacteria are claimed to have immunomodulating effects. Stimulation as well as suppression of T helper (Th)1 mediated immune responses, have been described for various strains. Experiments involving Lactobacillus casei Shirota (LcS) detected mainly enhancement of innate immune responses and promotion of Th1 mediated immune reactivity. To confirm and further investigate modulation of Th1 responses and development of autoimmune disease by LcS, the consequences of oral administration of LcS were assessed in several experiments. The effect of LcS varied between the different models. No modulation was found in the mitogen-induced cell proliferation and cytokine release assays in mesenteric lymph nodes of Wistar rats. LcS inhibited the Th1 mediated immune response in an adapted murine Local Lymph Node Assay (LLNA) in BALB/c mice, whereas experimental autoimmune encephalomyelitis (EAE) in Lewis rats was aggravated. These varying effects on Th1 responses indicate that beneficial as well as harmful effects on immune related disorders could occur after LcS consumption. Since microarray analysis is suggested to be more sensitive and predictive than functional tests, gene expression profiling was included as an alternative endpoint in the testing of immunomodulation. The detected gene expression profiles did not reflect the effects of LcS on the immune system. Microarray analysis may therefore have no more predictive value than immune function assays when investigating immunomodulation by probiotics. To gain further insight into effects of probiotics on immune function, experiments including cytokine assays and gene expression analysis combined with disease models could be useful.

Animals↗

Dietary quality and associated factors among adults living in the state of São Paulo, Brazil.

This study sought to analyze dietary quality and associated factors among adults living in regions of the State of São Paulo, Brazil. It was a cross-sectional population-based study of a sample of 3,454 adults ages 20 years and over who were included in the Household Health Survey. Dietary intake was measured by means of the 24-hour recall method, and dietary quality was assessed by means of the Healthy Eating Index (HEI), adapted to local realities. Probabilistic samples were obtained via multistage cluster samples from four regions in the State of São Paulo. Linear regression analyses were performed to evaluate the relationships between the HEI and the demographic, socioeconomic, and lifestyle variables. Among the individuals assessed, 5% had a good diet, 74% a diet that needed some degree of improvement, and 21% a poor diet. The means for HEI components were lowest for vegetables, fruits, and dairy products. The highest HEI scores were obtained by individuals who were nonsmokers, practiced physical activity, were retired, lived in houses or apartments, and had adequate living conditions surrounding them. In the multiple regression analysis, the variables of numbers of consumer durable goods, schooling of the head of the family, energy intake, and age had a positive association with the HEI. However, the association was inverse for the variables of smoking and body mass index. Higher dietary quality is associated with higher income, higher schooling level, better nutritional status, and being a nonsmoker. Knowledge of these factors is important for implementing programs for preventive nutrition or intervention.

Adult↗

Whole mitogenome profile of Pelung and Sentul chickens to reveal potency of Indonesian livestock genetic resources.

Native chickens are essential genetic resources in Indonesia, providing economic, cultural, and nutritional value with strong adaptability to local environments. Among these native chickens, Sentul and Pelung are recognized as national genetic resources due to dual-purpose and ornamental traits, respectively, but their whole mitogenome characterization remains limited. Therefore, this study aimed to assemble and analyze the whole mitogenome of Sentul and Pelung chickens as well as perform a comparison with 35 additional genomes from domestic chickens and jungle fowls across Asia. The experiment was carried out using next-generation sequencing and bioinformatics-based genome assembly and analysis. The results showed that both Sentul and Pelung genomes were 16,784 bp in length and contained the typical mitochondrial gene composition, including 13 protein-coding genes (PCGs), 22 transfer ribonucleic acids (tRNAs), two ribosomal ribonucleic acids (rRNAs), and a control region (D-loop). Furthermore, comparative analysis identified five single-nucleotide polymorphisms (SNPs) distinguishing the two breeds, located in ND1, COX1, COX2, ND4, and the D-loop region. Phylogenetic reconstruction based on whole mitochondrial sequences showed that Sentul and Pelung chickens belong to haplogroup D, alongside other native breeds and red jungle fowls from Indonesia and the Philippines.

Genetic diversity↗

Referral of chronic hepatitis B patients from primary to specialist care: making a simple guideline work.

BACKGROUND/AIMS: To evaluate a guideline selecting patients at the primary care level for referral to a specialist, to identify bottlenecks and subsequently implement and evaluate improvements. METHODS: Retrospective patient files analysis and a prospective cohort study. The study was conducted in Municipal Public Health Service (PHS), University Medical Center. Patients diagnosed with chronic hepatitis B virus (HBV) infection were referred to the PHS. Improvement of bottlenecks were identified in the referral chain, based on the guideline. Number of patients receiving correct advice, number of patients reaching the hospital for specialist care, time between notification of the PHS and final arrival in the hospital. RESULTS: The guideline for the referral of chronic HBV patients appeared to be appropriate, although one-third of the selected patients was not seen by the specialist. After the intervention more HBV patients (76 versus 61%) received correct advice from the PHS, and the number of HBV patients seen by the specialist increased by 18%. CONCLUSIONS: The referral guideline works, yet we could improve the efficiency of the guideline increasing the proportion of eligible patients reaching specialist care. In countries where mandatory reporting of HBV infections exists this guideline can be adapted to local health systems.

Cohort Studies↗

In-room CT techniques for image-guided radiation therapy.

Accurate patient setup and target localization are essential to advanced radiation therapy treatment. Significant improvement has been made recently with the development of image-guided radiation therapy, in which image guidance facilitates short treatment course and high dose per fraction radiotherapy, aiming at improving tumor control and quality of life. Many imaging modalities are being investigated, including x-ray computed tomography (CT), ultrasound imaging, positron emission tomography, magnetic resonant imaging, magnetic resonant spectroscopic imaging, and kV/MV imaging with flat panel detectors. These developments provide unique imaging techniques and methods for patient setup and target localization. Some of them are different; some are complementary. This paper reviews the currently available kV x-ray CT systems used in the radiation treatment room, with a focus on the CT-on-rails systems, which are diagnostic CT scanners moving on rails installed in the treatment room. We will describe the system hardware including configurations, specifications, operation principles, and functionality. We will review software development for image fusion, structure recognition, deformation correction, target localization, and alignment. Issues related to the clinical implementation of in-room CT techniques in routine procedures are discussed, including acceptance testing and quality assurance. Clinical applications of the in-room CT systems for patient setup, target localization, and adaptive therapy are also reviewed for advanced radiotherapy treatments.

Humans↗

Effective sizes of macroparasite populations: a conceptual model.

Effective population size (N(e)) is a crucial parameter in evolutionary biology because it controls genetic drift and the response to selection. Thus, N(e) influences evolutionary processes in parasites, such as speciation, host-race formation, local host adaptation and the evolution of drug resistance. However, N(e) is a parameter that is ignored almost completely in parasitology. Our goal is to provide a conceptual framework that facilitates future studies of the N(e) of macroparasites. The key feature of macroparasite populations is that breeders are subdivided into infrapopulations. We use a model of subdivided breeders to show how some basic demographic factors that control N(e) in all species could be estimated for macroparasites. An important conclusion is that several features of parasite life cycles probably function in concert to reduce N(e) below that expected in a single free-living population of equivalent census size.

Animals↗

Etiology of community acquired pneumonia among adult patients requiring hospitalization in Taiwan.

BACKGROUND: There has not been a comprehensive multi-center study investigating the microbial profile of community acquired pneumonia (CAP) in Taiwan. METHODS: A prospective study of adult CAP patients requiring hospitalization between December 2001 and April 2002 was carried out in 13 hospitals in Taiwan. Etiology was determined based on laboratory data from blood and sputum cultures plus serology from paired serum and urine antigen detection tests. RESULTS: Etiology was assigned to 99 (58.9%) of the 168 patients having the most complete data for etiology determination, with mixed infection in 21 (12.5%) patients. More than half (51.8%) of the patients were>60 years and 63.7% of the patients were males. The most common etiologic agent was Streptococcus pneumoniae (40, 23.8%), the majority (60%, 24 cases) of which was detected by positive urine antigen test. Other common agents included Mycoplasma pneumoniae (24, 14.3%), Chlamydia pneumoniae (12, 7.1%), Influenza A virus (11, 6.5%), Klebsiella pneumoniae (8, 4.8%) and Haemophilus influenzae (8, 4.8%). The prevalence of S. pneumoniae and M. pneumoniae was highest in patients>60 years (25/87, 28.7%), and<44 years (12/59, 19%), respectively; while K. pneumoniae comprised a larger proportion (4/22, 18%) in the 45-59 years group. CONCLUSIONS: S. pneumoniae was the most common etiology agent in adult patients hospitalized due to CAP in Taiwan and the spectrum of other major pathogens was similar to studies conducted elsewhere in the world. Empiric treatment recommendations developed in other parts of the world may be appropriately adapted for local use after taking into account local resistance profiles. Our data also support the recommendation that urine antigen test be added as an adjunct to adult CAP etiology diagnosis protocol.

Adolescent↗

Induction of secretory immunity and memory at mucosal surfaces.

Mucosal epithelia comprise an extensive vulnerable barrier which is reinforced by numerous innate defence mechanisms cooperating intimately with adaptive immunity. Local generation of secretory IgA (SIgA) constitutes the largest humoral immune system of the body. Secretory antibodies function both by performing antigen exclusion at mucosal surfaces and by virus and endotoxin neutralization within epithelial cells without causing tissue damage. SIgA is thus persistently containing commensal bacteria outside the epithelial barrier but can also target invasion of pathogens and penetration of harmful antigens. Resistance to toxin-producing bacteria such as Vibrio cholerae and enterotoxigenic Escherichia coli appears to depend largely on SIgA, and so does herd protection against horizontal faecal-oral spread of enteric pathogens under naïve or immunized conditions--with a substantial innate impact both on cross-reactivity and memory. Like natural infections, live mucosal vaccines or adequate combinations of non-replicating vaccines and mucosal adjuvants, give rise not only to SIgA antibodies but also to longstanding serum IgG and IgA responses. However, there is considerably disparity with regard to migration of memory/effector cells from mucosal inductive sites to secretory effector sites and systemic immune organs. Also, although immunological memory is generated after mucosal priming, this may be masked by a self-limiting response protecting the inductive lymphoid tissue in the gut. The intranasal route of vaccine application targeting nasopharynx-associated lymphoid tissue may be more advantageous for certain infections, but only if successful stimulation is achieved without the use of toxic adjuvants that might reach the central nervous system. The degree of protection obtained after mucosal vaccination ranges from reduction of symptoms to complete inhibition of re-infection. In this scenario, it is often difficult to determine the relative importance of SIgA versus serum antibodies, but infection models in knockout mice strongly support the notion that SIgA exerts a decisive role in protection and cross-protection against a variety of infectious agents. Nevertheless, relatively few mucosal vaccines have been approved for human use, and more basic work is needed in vaccine and adjuvant design, including particulate or live-vectored combinations.

Animals↗

Sinusoid = light bar + dark bar?

A sinusoidal grating can be viewed as a series of light and dark bars. Here we measure the contrast discrimination thresholds for light and dark bars individually, and find that the contrast discrimination thresholds for the whole sinusoid can be explained as ideal summation of the light and dark bar thresholds. We propose a model for light bar, dark bar, and sinusoidal contrast discrimination which involves local light adaptation and multiplicative noise. The model accounts for the data very well, and also accounts for contrast discrimination of light and dark edges.

Adaptation, Ocular↗

A perturbed two-level model for exciton trapping in small photosynthetic systems.

The study of exciton trapping in photosynthetic systems provides significant information about migration kinetics within the light harvesting antenna (LHA) and the reaction center (RC). We discuss two random walk models for systems with weakly coupled pigments, with a focus on the application to small systems (10-40 pigments/RC). Details of the exciton transfer to and from the RC are taken into consideration, as well as migration within the LHA and quenching in the RC. The first model is obtained by adapting earlier local trap models for application to small systems. The exciton lifetime is approximated by the sum of three contributions related to migration in the LHA, trapping by the RC, and quenching within the RC. The second model is more suitable for small systems and regards the finite rate of migration within the LHA as a perturbation of the simplified model, where the LHA and the RC are each represented by a single pigment level. In this approximation, the exciton lifetime is the sum of a migration component and a single nonlinear expression for the trapping and quenching of the excitons. Numerical simulations demonstrate that both models provide accurate estimates of the exciton lifetime in the intermediate range of 20-50 sites/RC. In combination, they cover the entire range of very small to very large photosynthetic systems. Although initially intended for regular LHA lattices, the models can also be applied to less regular systems. This becomes essential as more details of the structure of these systems become available. Analysis with these models indicates that the excited state decay in LH1 is limited by the average rate at which excitons transfer to the RC from neighboring sites in the LHA. By comparing this to the average rate of transfer within the LHA, various structural models that have been proposed for the LH1 core antenna are discussed.

Bacterial Proteins↗

Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation.

The physiological function of a recently cloned splice variant of insulin-like growth factor-I (IGF-I; mechano growth factor (MGF)) was studied using an in vitro cell model. Unlike mature IGF-I, the distinct E domain of MGF inhibits terminal differentiation whilst increasing myoblast proliferation. Blocking the IGF-I receptor with a specific antibody indicated that the function of MGF E domain is mediated via a different receptor. The results provide a basis for localized tissue adaptation and helps explain why loss of muscle mass occurs in the elderly and in dystrophic muscle in which MGF production is markedly affected.

Alternative Splicing↗

The FIGO Save the Mothers Initiative: the Ethiopia-Sweden collaboration.

The overall goal of the FIGO Save the Mothers Fund was to establish basic and comprehensive emergency obstetric care (EmOC) with the specific objectives of increasing the availability and utilization of quality obstetric care as measured by the UN indicators. As a result of this commitment by FIGO, the Ethiopian Society of Obstetricians and Gynecologists (ESOG) launched the Save the Mothers Project (SMP) in West Showa Zone (WSZ), Ethiopia in 1998 to implement and test a demonstration project and evaluate the feasibility and impact of the intervention. The overall objectives matched FIGO's-reducing maternal deaths by promoting the availability, access and utilization of EmOC services for women with complications of pregnancy and childbirth. The intervention package included capacity building as a major activity, and physicians and other service providers from Ambo Hospital, Shenen and Ijaji Health Centers were trained in EmOC. This was intended to combat the high staff turnover in the area. Equipment, materials and supplies were also provided to the demonstration sites to enable them provide basic and comprehensive EmOC services. The interventions, begun in 1999, led to improvements in availability, utilization and met need, which suggests that such an approach may eventually lead to the reduction of maternal deaths. The cesarean section rate for Ambo Hospital increased from 3.7% in 1998 to 17.3% in 2001--an almost six-fold increase. At Ambo Hospital both the total number of deliveries and cases admitted with obstetric complications have increased from baseline. Patients with obstructed labor comprise 39% of all obstetric patients making it the leading cause of hospitalization. Obstetric hemorrhage comes next with 24% of all admissions. The case fatality rate (CFR) (for direct maternal deaths) decreased from 7.2% at baseline, to 4.6% in 2001--showing a definite trend of improvement. Currently, there is 24-h EmOC service at Ambo Hospital where an obstetrician and general medical practitioners with EmOC training are responsible for the service. Shenen and Ijaji health Centers are upgraded in terms of training of staff members, provision of equipment and supplies, and regular supervision so that the community in these areas has access to basic EmOC services. To replicate similar activities, in a setting like ours, EmOC projects have to be low cost to attract decision-makers. The SMP used almost US dollars 100,000 over 3 years to ensure availability of EmOC services for women in WSZ. A favorable political climate such as maintenance of relative peace, and flexibility in adapting to local conditions also contributed to the success of the SMP.

Cesarean Section↗

Evaluation of transplant procurement management courses: an educational project as a tool for the optimization of transplant coordination.

The process of obtaining organs and tissues includes a series of procedures and skills that are fundamental to obtain a large number and high quality of transplants. Health professionals involved in transplant coordination require robest and comprehensive training to integrate the donation-transplantation process within the clinical health care field. Based on a learning-through-experience model, Transplant Procurement Management (TPM) designed various courses adapted to local educational need to train transplant coordinators, to increase active donor detection, and to promote a positive attitude towards donation; namely, Advanced, Introductory and New Life Cycle courses respectively. Moreover, TPM has coordinated international programs (INTERCATT and INTERITALY). Since 1991, the model has included 29 Advanced courses (1215 participants), 22 Introductory courses (575 pupils), and 7 New Life Cycle courses (more than 400 attendees). The Advanced courses were attended by medical (intensive care unit, nephrology, and others) and nursing professionals. Assessment of the educational program showed achievement of teaching objectives. The evaluation averages above 3.5 (scale, 1-5) for content, presentation, and ability to answer questions. Likewise, the program's organization showed an average score of 4.4. The acquired knowledge was assessed by means of a self-evaluation test (correct answers >69%). Practical skills assessed through direct observation showed an average of 7 (scale, 1-10). The TPM educational program offers a range of necessary knowledge and skills to increase organ donation. Health professionals concerned about the organ shortage may find TPM training useful to increase their knowledge.

Curriculum↗

Interactions between flicker thresholds and luminance pedestals.

We investigated the interactions between flicker thresholds and luminance pedestals using threshold versus contrast (TvC) and method of constant stimuli paradigms. High amplitude luminance pedestals were found to elevate flicker thresholds, but low amplitude luminance pedestals were unable to reduce flicker thresholds. Luminance pedestals elevated flicker thresholds more at low temporal frequencies. A simple model based on local light adaptation was able to capture the general form of the TvC functions. Our results suggest that flicker thresholds derived in the presence of a luminance pedestal (luminance-pedestal flicker) may vary from those obtained by modulating about a mean luminance (mean-modulated flicker).

Adaptation, Ocular↗

Multiple processes mediate flicker sensitivity.

By systematically manipulating the luminance of a flickering spot and the area immediately surrounding it, we investigated why thresholds from flickering stimuli that cause a change in average luminance are elevated relative to those from stimuli with no luminance change. Threshold elevation resulted from local light adaptation and from temporal-frequency-specific interactions between the spot and its surround: at low frequencies, the contrast between the spot and the surround elevated thresholds, whereas at high frequencies, dark adaptation within the surround elevated thresholds. Our findings suggest that two common ways of determining temporal sensitivity may give markedly different outcomes.

Adaptation, Ocular↗

Incidence of 1/29 translocation in Bolivian Creole and Brahman Yacumeño cattle.

In Bolivia, four different Creole cattle breeds can be found, as well as other European and Zebu breeds adapted to local environments. The relationship between the occurrence of the 1/29 translocation and subfertility is well known, and analysis of Y chromosome morphology is useful to determine a possible introgression with Bos indicus. The incidence of the 1/29 translocation was analyzed in four Bolivian Creole cattle breeds and the Brahman Yacumeño population, as well as on four farms with phenotypical Creole-type cattle. In 259 (164 dams and 95 sires) Bolivian Creole cattle, 10.42% of the individuals demonstrated the 1/29 translocation, with a variation from 0 to 28.20% between the breeds. In contrast, 43 (19 dams and 24 sires) Yacumeño Brahman and the Creole-type cattle did not show the centric fusion. The highly significant differences between Creole cattle breeds in relation to the incidence of 1/29 translocation could be a consequence of factors such as founder group, genetic drift, and selection. The low frequency observed in the Saavedreñio Creole dairy cattle might be explained by its breeding under a more intensive system, and selection according to milk yield and fertility traits. Finally, no relation between acrocentric Y chromosomes and 1/29 translocation was observed.

Animals↗

Relation between age, femoral neck cortical stability, and hip fracture risk.

BACKGROUND: Hip fracture risk rises 100 to 1000-fold over 60 years of ageing. Loss of resistance to bending is not a major feature of normal ageing of the femoral neck. Another cause of fragility is local buckling or elastic instability. Bones adapt to their local experience of mechanical loading. The suggestion that bipedalism allows thinning of the underloaded superolateral femoral neck cortex arises from the failure of walking to transmit much mechanical load to this region. We aimed to measure whether elastic instability increases greatly with age since it might trigger hip fracture in a sideways fall. METHODS: We measured with computed tomography the distribution of bone in the mid-femoral neck of 77 proximal femurs from people who died suddenly aged 20-95 years. We then calculated the critical stress, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall, as a threshold for elastic instability. FINDINGS: With normal ageing, this thin cortical zone in the upper femoral neck became substantially thinner. Relative to mean values at age 60 years, female cortical thickness declined by 6.4% (SD 1.1) per decade (p<0.0001), and critical stress by 13.2% (4.3) per decade (p=0.004) in the superoposterior octant compressed most in a sideways fall. Similar, but significantly smaller, effects were evident in men (p=0.004). This thinning compromised the capacity of the femur to absorb energy independently of osteoporosis. Patients with hip fracture had further reduced stability. INTERPRETATION: As women age, hip fragility increases because underloading of the superolateral cortex leads to atrophic thinning. Because walking does not sufficiently load the upper femoral neck, the fragile zones in healthy bones may need strengthening, for example with more well targeted exercise.

Absorptiometry, Photon↗

The cost of developing and implementing a pathway for Congestive Heart Failure: not an inexpensive journey.

This article describes the cost of developing and implementing an integrated care pathway (ICP) for Congestive Heart Failure. Costs were tracked prospectively and allocated to either development or implementation. The development took 1,980 hours of staff time at a salary cost of $67,800. The ICP implementation took 2,083 hours of personnel time at a salary cost of $66,900. Even though an available pathway was adapted for local use, a substantial amount of time and money was required. This article may be useful to others who are interested in monitoring costs of pathways.

Critical Pathways↗