Mushroom β-Glucan May Immunomodulate the Tumor-Associated Macrophages in the Lewis Lung Carcinoma.
The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides.


Genotypic and phenotypic characteristics of Escherichia coli involved in transfusion-transmitted bacterial infections: implications for preventive strategies.
Transfusion-transmitted bacterial infections (TTBIs) are the main residual infectious complications of transfusions. Escherichia coli and platelet (PLT) concentrates may be epidemiologically associated, leading to severe, if not lethal, TTBIs. We investigated the genotypic and phenotypic reasons for this clinically deleterious combination. We investigated a French national E. coli strain collection related to six independent episodes of TTBIs. Their phenotypic characterizations included antibiotic susceptibility testing, growth testing under different culture conditions, serum survival assays, and virulence in a sepsis mouse model. Their genotypic characterizations included polymerase chain reaction phylotyping, whole genome sequencing, and a subsequent in silico analysis. We highlighted a selection process of highly extraintestinal virulent strains, mainly belonging to the B2 phylogroup, adapted to the hostile environment (high citrate concentration and a bactericidal serum effect) of apheresis-collected platelet concentrates (PCs). Compared to controls, the E. coli TTBI strains grew faster in the PCs due to a superior ability to capture iron. The in vitro growth performances were highly compatible with blood-derived product real-life conditions, including storage conditions and delays. The consistent serum resistance of TTBI strains promotes their survival in both the donor's and the receiver's blood and in the PCs. This study pointed out that E. coli strains responsible for TTBI exhibit very specific traits. They belong to the extraintestinal pathogenic phylogroups and have a high intrinsic virulence. They can be resistant to complement, capture iron, and grow in the apheresis-collected PCs. These findings therefore support the reinforcement of the postdonation information.


Inhibition of sodium-glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization.
The goal of the present study was to evaluate the effects of SGLT2i on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in normal, metabolically healthy swine. Lean swine received placebo or canagliflozin (300 mg PO) 24 h prior to and the morning of an invasive physiologic study protocol. Hemodynamic and cardiac function measurements were obtained at baseline, during a 30-min complete occlusion of the circumflex coronary artery, and during a 2-h reperfusion period. Blood pressure, heart rate, coronary flow, and myocardial oxygen consumption were unaffected by canagliflozin treatment. Ventricular volumes remained unchanged in controls throughout the protocol. At the onset of ischemia, canagliflozin produced acute large increases in left ventricular end-diastolic and systolic volumes which returned to baseline with reperfusion. Canagliflozin-mediated increases in end-diastolic volume were directly associated with increases in stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial uptake of glucose, lactate, free fatty acids or ketones, were noted between treatment groups at any time. In separate experiments using a longer 60 min coronary occlusion followed by 2 h of reperfusion, canagliflozin increased end-diastolic volume and stroke volume and significantly diminished myocardial infarct size relative to control swine. These data demonstrate that SGLT2i with canagliflozin preserves cardiac contractile function and efficiency during regional myocardial ischemia and provides ischemia protection independent of alterations in myocardial substrate utilization.


Loss of the SMRT/NCoR2 corepressor correlates with JAG2 overexpression in multiple myeloma.
Multiple myeloma (MM) is a clonal B-cell neoplasm that accounts for 10% of all malignant hematologic neoplasms and that affects terminally differentiated B cells (i.e., plasma cells). It is now well recognized that the cytokine interleukin-6 (IL-6) is a major cytokine that promotes the proliferation of malignant plasma cells in MM. The IL-6 gene can be regulated by the NOTCH genes products. We have previously shown that the NOTCH ligand, JAG2, is overexpressed in MM. To investigate the mechanism(s) leading to JAG2 overexpression in MM, we assessed potential epigenetic modifications of the JAG2 promoter. We showed that the JAG2 promoter region is aberrantly acetylated in MM cell lines and patient samples. The acetylation state of histones is regulated by the recruitment of histone deacetylases (HDAC). HDACs are typically recruited to promoter regions through interaction with nuclear corepressors such as SMRT. SMRT levels were therefore investigated. Interestingly, MM cell lines and patient samples presented significantly reduced SMRT levels. The experiments suggest a correlation between constitutive acetylation of the JAG2 core promoter in the MM cell lines and reduced levels of the SMRT corepressor that recruits HDAC to promoter regions. Finally, SMRT function restoration induced JAG2 down-regulation as well as MM cell apoptosis.


A novel fungal family of oligopeptide transporters identified by functional metatranscriptomics of soil eukaryotes.
Functional environmental genomics has the potential to identify novel biological functions that the systematic sequencing of microbial genomes or environmental DNA may fail to uncover. We targeted the functions expressed by soil eukaryotes using a metatranscriptomic approach based on the use of soil-extracted polyadenylated messenger RNA to construct environmental complementary DNA expression libraries. Functional complementation of a yeast mutant defective in di/tripeptide uptake identified a novel family of oligopeptide transporters expressed by fungi. This family has a patchy distribution in the Basidiomycota and Ascomycota and is present in the genome of a Saccharomyces cerevisiae wine strain. High throughput phenotyping of yeast mutants expressing two environmental transporters showed that they both displayed broad substrate specificity and could transport more than 60-80 dipeptides. When expressed in Xenopus oocytes one environmental transporter induced currents upon dipeptide addition, suggesting proton-coupled co-transport of dipeptides. This transporter was also able to transport specifically cysteine. Deletion of the two copies of the corresponding gene family members in the genome of the wine yeast strain severely reduced the number of dipeptides that it could assimilate. These results demonstrate that these genes are functional and can be used by fungi to efficiently scavenge the numerous, low concentration, oligopeptides continuously generated in soils by proteolysis.


Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.
To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non-adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia.


The origin and evolution of ARGFX homeobox loci in mammalian radiation.
Many homeobox genes show remarkable conservation between divergent animal phyla. In contrast, the ARGFX (Arginine-fifty homeobox) homeobox locus was identified in the human genome but is not present in mouse or invertebrates. Here we ask when and how this locus originated and examine its pattern of molecular evolution. Phylogenetic and phylogenomic analyses suggest that ARGFX originated by gene duplication from Otx1, Otx2 or Crx during early mammalian evolution, most likely on the stem lineage of the eutherians. ARGFX diverged extensively from its progenitor homeobox gene and its exons have been functional and subject to purifying selection through much of placental mammal radiation. Surprisingly, the coding region is disrupted in most mammalian genomes analysed, with human being the only mammal identified in which the full open reading frame is retained. Indeed, we describe a transcript from human testis that has the potential to encode the full deduced protein. The unusual pattern of evolution suggests that the ARGFX gene may encode a functional RNA or alternatively it may have 'flickered' between functional and non-functional states in the evolutionary history of mammals, particularly in the period when many mammalian lineages diverged within a relatively short time span.


Silica in developing epidermal cells of Avena internodes: electron microprobe analysis.
Silica is present in significant amount in mature guard and subsidiary cells of stomata, in trichomes and silica cells, and in the walls of long eidermal cells of Avena. No silica was detectable in cork cells of cork-silica cell pairs. Silica must be accumulated in these specialized epidermal cells quite rapidly.


Analyzing Knowledge Retrieval Impairments Associated with Alzheimer's Disease Using Network Analyses.
A defining characteristic of Alzheimer's disease is difficulty in retrieving semantic memories, or memories encoding facts and knowledge. While it has been suggested that this impairment is caused by a degradation of the semantic store, the precise ways in which the semantic store is degraded are not well understood. Using a longitudinal corpus of semantic fluency data (listing of items in a category), we derive semantic network representations of patients with Alzheimer's disease and of healthy controls. We contrast our network-based approach with analyzing fluency data with the standard method of counting the total number of items and perseverations in fluency data. We find that the networks of Alzheimer's patients are more connected and that those connections are more randomly distributed than the connections in networks of healthy individuals. These results suggest that the semantic memory impairment of Alzheimer's patients can be modeled through the inclusion of spurious associations between unrelated concepts in the semantic store. We also find that information from our network analysis of fluency data improves prediction of patient diagnosis compared to traditional measures of the semantic fluency task.


VEGF signals induce trailblazer cell identity that drives neural crest migration.
Embryonic neural crest cells travel in discrete streams to precise locations throughout the head and body. We previously showed that cranial neural crest cells respond chemotactically to vascular endothelial growth factor (VEGF) and that cells within the migratory front have distinct behaviors and gene expression. We proposed a cell-induced gradient model in which lead neural crest cells read out directional information from a chemoattractant profile and instruct trailers to follow. In this study, we show that migrating chick neural crest cells do not display distinct lead and trailer gene expression profiles in culture. However, exposure to VEGF in vitro results in the upregulation of a small subset of genes associated with an in vivo lead cell signature. Timed addition and removal of VEGF in culture reveals the changes in neural crest cell gene expression are rapid. A computational model incorporating an integrate-and-switch mechanism between cellular phenotypes predicts migration efficiency is influenced by the timescale of cell behavior switching. To test the model hypothesis that neural crest cellular phenotypes respond to changes in the VEGF chemoattractant profile, we presented ectopic sources of VEGF to the trailer neural crest cell subpopulation and show diverted cell trajectories and stream alterations consistent with model predictions. Gene profiling of trailer cells that diverted and encountered VEGF revealed upregulation of a subset of 'lead' genes. Injection of neuropilin1 (Np1)-Fc into the trailer subpopulation or electroporation of VEGF morpholino to reduce VEGF signaling failed to alter trailer neural crest cell trajectories, suggesting trailers do not require VEGF to maintain coordinated migration. These results indicate that VEGF is one of the signals that establishes lead cell identity and its chemoattractant profile is critical to neural crest cell migration.


Erythromycin-resistant Streptococcus pyogenes in Argentina.
Erythromycin (ERY) resistance in Streptococcus pyogenes has recently emerged as a problem of growing concern all through the world. We are presenting the comparison of results of the continuous surveillance of erythromycin resistance in S. pyogenes performed since 1989 in the Hospital de Pediatría J.P. Garrahan of Buenos Aires City, with independently observed rates in other five centers of Buenos Aires and seven centers of six other Argentinian cities, obtained between 1999 and 2001. A significant increase of erythromycin resistance was observed among S. pyogenes isolated in the Hospital Garrahan (6.6% in 1998-1999 to 9.9% in 2000). Similar trends were also detected in other centers of other Argentinian cities when recent data were compared to results of a multicenter study performed in 1995. However, lower rates of resistance were recorded in Mendoza, Cipolletti and Neuquén in comparison with data of 1995, 1998 and 1998 respectively. The reason of such decreasing resistance rates deserves to be investigated. The average of ERY-resistance rates obtained in the surveyed centers was 6.7% (range 0.5-14.1%). Control of antimicrobial use should be performed to warrant the future effectiveness of macrolide antibiotics regarding the positive association between use and resistance. These results also suggest that susceptibility tests for macrolides should be performed whenever S. pyogenes is isolated in Argentina.


Central line-related sepsis in acute burn patients.
A retrospective review of all 443 burn patients admitted during a 13-month period from October 1, 1992 to October 31, 1993, was completed. Of these, 8 were transferred and eliminated from the study. Twenty-two patients who were felt to be terminal on admission and did not have blood cultures were included in the demographic data but were excluded from subsequent statistical analysis. One hundred ten patients had central venous lines (CVLs). Three patients with CVLs were transferred, thus leaving 107 patients with CVLs for statistical analysis. Additionally, 17 of the aforementioned terminal patients who had CVLs and 1 patient with a CVL who had documented sepsis before CVL insertion were excluded, leaving 89 patients with CVLs used in statistical analysis. Mean burn surface for those with central lines was 35.8 per cent, and for those without, 10.9 per cent. Sixty-four patients (59.8%) with a central line had inhalation injuries, as did 18 patients (5.5%) without. The number of lines per patient varied from 1 to 7. Sixty-one patients had one line, 46 had more than one. The total number of central line days for the entire group was 1749. The mean number of central line days per patient was 16.3. The mean number of line days per catheter was 8.48. The mortality rate for the 107 patients with a central line was 34 (32.7%). Mortality for all patients was 41 (9.4%). The incidence of sepsis increased with increasing number of central line days and increasing number of central line changes, but the effect of these two factors on the incidence of sepsis could not be studied separately, as they are highly correlated with each other. The most commonly recovered organisms were various types of Staphylococcus. Polymicrobial infections were common. There were 51 subclavian, 17 internal jugular, and 135 femoral catheters inserted. By logistic regression analysis, there was no statistically significant difference in the incidence of sepsis between upper- and lower-body CVL sites. Twenty-four patients (22.4%) with a CVL and one or more positive blood cultures were felt to have demonstrated sepsis. Some had more than one septic episode while lines were in place, reported as separate patients but not as separate septic episodes.


Nutritional supplements in support of resistance exercise to counter age-related sarcopenia.
Age-related sarcopenia, composed of myopenia (a decline in muscle mass) and dynapenia (a decline in muscle strength), can compromise physical function, increase risk of disability, and lower quality of life in older adults. There are no available pharmaceutical treatments for this condition, but evidence shows resistance training (RT) is a viable and relatively low-cost treatment with an exceptionally positive side effect profile. Further evidence suggests that RT-induced increases in muscle mass, strength, and function can be enhanced by certain foods, nutrients, or nutritional supplements. This brief review focuses on adjunctive nutritional strategies, which have a reasonable evidence base, to enhance RT-induced gains in outcomes relevant to sarcopenia and to reducing risk of functional declines.


"Bioconvection Patterns" in Cultures of Free-Swimming Organisms.
The moving polygonal patterns in dense cultures of Tetrahymena and other ciliates and flagellates look like "Benard cells," but are not due to thermal convection. They seem to be due to a similar dynamic instability that occurs when the energy input is internal and mechanical. The high concentration in the patterns may be useful in fertilization.


Long-range surface magnetoplasmon on thin plasmon films in the Voigt configuration.
This study elucidates the characteristics of a long-range surface magnetoplasmon (LRSMP) that propagates on a plasmon film with the Voigt configuration. Particle-in-cell (PIC) simulations and theoretical analyses are performed. Simulation results indicate that LRSMP has non-symmetrical fields. The proposed scheme also verifies the non-reciprocal properties of LRSMP as the direction of an applied external magnetic field is reversed. When surface waves propagate on a plasmon film across an interface on one side of which long-range surface plasmon (LRSP) is allowed while on the other side of which LRSMP is allowed, the interface behaves similar to a defect and transforms the surface waves into radiation modes owing to the mismatch between the field patterns of LRSP and LRSMP. Furthermore, PIC simulation results confirm the presence of a new high-frequency LRSMP whose frequency exceeds the plasma frequency and lacks a LRSP counterpart.


Mortality in British vegetarians: review and preliminary results from EPIC-Oxford.
Three prospective studies have examined the mortality of vegetarians in Britain. We describe these 3 studies and present preliminary results on mortality from the European Prospective Investigation into Cancer and Nutrition-Oxford (EPIC-Oxford). The Health Food Shoppers Study and the Oxford Vegetarian Study were established in the 1970s and 1980s, respectively; each included about 11 000 subjects and used a short questionnaire on diet and lifestyle. EPIC-Oxford was established in the 1990s and includes about 56 000 subjects who completed detailed food frequency questionnaires. Mortality in all 3 studies was followed though the National Health Service Central Register. Overall, the death rates of all the subjects in all 3 studies are much lower than average for the United Kingdom. Standardized mortality ratios (95% CIs) for all subjects were 59% (57%, 61%) in the Health Food Shoppers Study, 52% (49%, 56%) in the Oxford Vegetarian Study, and 39% (37%, 42%) in EPIC-Oxford. Comparing vegetarians with nonvegetarians within each cohort, the death rate ratios (DRRs), adjusted for age, sex and smoking, were 1.03 (0.95, 1.13) in the Health Food Shoppers Study, 1.01 (0.89, 1.14) in the Oxford Vegetarian Study, and 1.05 (0.86, 1.27) in EPIC-Oxford. DRRs for ischemic heart disease in vegetarians compared with nonvegetarians were 0.85 (0.71, 1.01) in the Health Food Shoppers Study, 0.86 (0.67, 1.12) in the Oxford Vegetarian Study, and 0.75 (0.41, 1.37) in EPIC-Oxford. The mortality of both the vegetarians and the nonvegetarians in these studies is low compared with national rates. Within the studies, mortality for major causes of death was not significantly different between vegetarians and nonvegetarians, but the nonsignificant reduction in mortality from ischemic heart disease among vegetarians was compatible with the significant reduction previously reported in a pooled analysis of mortality in Western vegetarians.


A conceptual model linking functional gene expression and reductive dechlorination rates of chlorinated ethenes in clay rich groundwater sediment.
We used current knowledge of cellular processes involved in reductive dechlorination to develop a conceptual model to describe the regulatory system of dechlorination at the cell level; the model links bacterial growth and substrate consumption to the abundance of messenger RNA of functional genes involved in the dechlorination process. The applicability of the model was tested on a treatability study of biostimulated and bioaugmented microcosms. Using quantitative real time PCR, high-resolution expression profiles of the functional reductive dehalogenase genes bvcA and vcrA were obtained during two consecutive dechlorination events of trichlorethene, cis-dichlorethene and vinyl chloride. Up-regulation of the bvcA (for the biostimulated microcosms) and vcrA (for the bioaugmented microcosms) gene expression fitted well with high rates of dechlorination of vinyl chloride, while no known transcripts could be measured during trichloroethene and cis-dichlorethene dechlorination. Maximum concentrations of 2.1 and 1.7 transcripts per gene of the bvcA and vcrA genes, respectively, were measured at the same time points as maximum dechlorination rates were observed. The developed model compared well with the experimental data for both biostimulated and bioaugmented microcosms under non-steady state conditions and was supported by results from a recently published study under steady state conditions.


Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation.
Shaping a developing organ or embryo relies on the spatial regulation of cell division and shape. However, morphogenesis also occurs through changes in cell-neighbourhood relationships produced by intercalation. Intercalation poses a special problem in epithelia because of the adherens junctions, which maintain the integrity of the tissue. Here we address the mechanism by which an ordered process of cell intercalation directs polarized epithelial morphogenesis during germ-band elongation, the developmental elongation of the Drosophila embryo. Intercalation progresses because junctions are spatially reorganized in the plane of the epithelium following an ordered pattern of disassembly and reassembly. The planar remodelling of junctions is not driven by external forces at the tissue boundaries but depends on local forces at cell boundaries. Myosin II is specifically enriched in disassembling junctions, and its planar polarized localization and activity are required for planar junction remodelling and cell intercalation. This simple cellular mechanism provides a general model for polarized morphogenesis in epithelial organs.


Uniform SiGe/Si quantum well nanorod and nanodot arrays fabricated using nanosphere lithography.
This study fabricates the optically active uniform SiGe/Si multiple quantum well (MQW) nanorod and nanodot arrays from the Si0.4Ge0.6/Si MQWs using nanosphere lithography (NSL) combined with the reactive ion etching (RIE) process. Compared to the as-grown sample, we observe an obvious blueshift in photoluminescence (PL) spectra for the SiGe/Si MQW nanorod and nanodot arrays, which can be attributed to the transition of PL emission from the upper multiple quantum dot-like SiGe layers to the lower MQWs. A possible mechanism associated with carrier localization is also proposed for the PL enhancement. In addition, the SiGe/Si MQW nanorod arrays are shown to exhibit excellent antireflective characteristics over a wide wavelength range. These results indicate that SiGe/Si MQW nanorod arrays fabricated using NSL combined with RIE would be potentially useful as an optoelectronic material operating in the telecommunication range.


Crossing the chasm: information technology to biomedical informatics.
Accelerating the translation of new scientific discoveries to improve human health and disease management is the overall goal of a series of initiatives integrated in the National Institutes of Health (NIH) "Roadmap for Medical Research." The Clinical and Translational Science Award (CTSA) program is, arguably, the most visible component of the NIH Roadmap providing resources to institutions to transform their clinical and translational research enterprises along the goals of the Roadmap. The CTSA program emphasizes biomedical informatics as a critical component for the accomplishment of the NIH's translational objectives. To be optimally effective, emerging biomedical informatics programs must link with the information technology platforms of the enterprise clinical operations within academic health centers.This report details one academic health center's transdisciplinary initiative to create an integrated academic discipline of biomedical informatics through the development of its infrastructure for clinical and translational science infrastructure and response to the CTSA mechanism. This approach required a detailed informatics strategy to accomplish these goals. This transdisciplinary initiative was the impetus for creation of a specialized biomedical informatics core, the Center for Biomedical Informatics (CBI). Development of the CBI codified the need to incorporate medical informatics including quality and safety informatics and enterprise clinical information systems within the CBI. This article describes the steps taken to develop the biomedical informatics infrastructure, its integration with clinical systems at one academic health center, successes achieved, and barriers encountered during these efforts.


Reduced Contrast Sensitivity is Associated With Elevated Equivalent Intrinsic Noise in Type 2 Diabetics Who Have Mild or No Retinopathy.
To evaluate explanations for contrast sensitivity (CS) losses in subjects who have mild nonproliferative diabetic retinopathy (NPDR) or no diabetic retinopathy (NDR) by measuring and modeling CS in luminance noise. Ten diabetic subjects with NDR, 10 with mild NPDR, and 10 age-equivalent nondiabetic controls participated. Contrast threshold energy (Et) was measured for letters presented in the absence of noise (Et0) and in four levels of luminance noise. Data were fit with the linear amplifier model to estimate inferred noise level within the visual pathway (Neq) and sampling efficiency (ability to use stimulus information optimally). Et0, Neq, and efficiency were compared to clinical characteristics. Neq was correlated with Et0 for the diabetic subjects (r = 0.93, P < 0.001) and ranged from normal to 12-times the upper limit of normal. ANOVA indicated significant differences among the subject groups for Et0 and Neq (both F > 11.92, P < 0.001). Et0 and Neq were elevated for the mild NPDR group compared to the control and NDR groups (all t > 3.89, P ≤ 0.001); the NDR and control groups did not differ significantly (all t < 0.61, P > 0.55). There were no significant efficiency differences among the groups (F = 1.29, P = 0.29). Neq was correlated significantly with disease duration, microperimetric sensitivity, and Pelli-Robson CS. Elevated contrast threshold may be associated with increased intrinsic noise in early-stage diabetic subjects. Results suggest that noise-based CS measurements can provide important information about early neural dysfunction in these individuals.


Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae.
Natural transformation is a widespread mechanism for genetic exchange in bacteria. Aminoglycoside and fluoroquinolone antibiotics, as well as mitomycin C, a DNA-damaging agent, induced transformation in Streptococcus pneumoniae. This induction required an intact competence regulatory cascade. Furthermore, mitomycin C induction of recA was strictly dependent on the development of competence. In response to antibiotic stress, S. pneumoniae, which lacks an SOS-like system, exhibited genetic transformation. The design of antibiotherapy should take into consideration this potential of a major human pathogen to increase its rate of genetic exchange in response to antibiotics.


Challenges to the development of vaccines to hepatitis C virus that elicit neutralizing antibodies.
Despite 20 years of research, a vaccine to prevent hepatitis C virus (HCV) infection has not been developed. A vaccine to prevent HCV will need to induce broadly reactive immunity able to prevent infection by the 7 genetically and antigenically distinct genotypes circulating world-wide. HCV encodes two surface exposed glycoproteins, E1 and E2 that function as a heterodimer to mediate viral entry. Neutralizing antibodies (NAbs) to both E1 and E2 have been described with the major NAb target being E2. The function of E2 is to attach virions to host cells via cell surface receptors that include, but is not limited to, the tetraspanin CD81 and scavenger receptor class B type 1. However, E2 has developed a number of immune evasion strategies to limit the effectiveness of the NAb response and possibly limit the ability of the immune system to generate potent NAbs in natural infection. Hypervariable regions that shield the underlying core domain, subdominant neutralization epitopes and glycan shielding combine to make E2 a difficult target for the immune system. This review summarizes recent information on the role of NAbs to prevent HCV infection, the targets of the NAb response and structural information on glycoprotein E2 in complex with neutralizing antibodies. This new information should provide a framework for the rational design of new vaccine candidates that elicit highly potent broadly reactive NAbs to prevent HCV infection.


Having to focus on doing rather than being-nurse assistants' experience of palliative care in municipal residential care settings.
Palliative care should be provided, irrespective of setting to all patients facing a life-threatening illness and to their families. The situation and needs of older people differ from those of younger people since they often have several co-existing diseases and health complaints. This implies an extensive need for care and for longer periods of palliative care. The main providers of palliative care for older people are nurse assistants, who are also those with the shortest education. The aim of this study was to illuminate nurse assistants' experience of palliative care for older people in residential care. The study had an explorative, descriptive design. Thirteen residential care units in three different districts in a large city in southern Sweden. Twenty-five nurse assistants selected to represent variations in age, gender workplace and work experience. Data were collected from six focus-group interviews and subjected to content analysis to gain an understanding of the phenomenon. The nurse assistants described palliative care as a contrast to the everyday care they performed in that they had a legitimate possibility to provide the care needed and a clear assignment in relation to relatives. Palliative care also meant having to face death and dying while feeling simultaneous that it was unnatural to talk about death and having to deal with their own emotions. They emphasised that they were in need of support and experienced leadership as invisible and opaque, but gained strength from being recognized. In order to support nurse assistants in providing high quality end-of-life care, more focus is needed on the trajectory of older peoples' dying, on the importance of involving relatives throughout the period of care provision, and on support when encountering death and dying. There is also a need for engaged care leaders, both registered nurses and managers, to recognize the work of nurse assistants and to support care provision for older people within the framework of palliative care philosophy.


Copayments and Emergency Department Use Among Adult Medicaid Enrollees.
A number of state Medicaid programs have recently proposed or implemented new or increased copayments for nonemergent emergency department (ED) visits. Evidence suggests that copayments generally reduce the level of healthcare utilization, although there is little specific evidence regarding the effectiveness of copayments in reducing nonurgent ED use among Medicaid enrollees or other low-income populations. Encouraging efficient and appropriate use of healthcare services will be of particular importance for Medicaid programs as they expand under the Patient Protection and Affordable Care Act. This analysis uses national data from 2001 to 2009 to examine the effect of copayments on nonurgent ED utilization among nonelderly adult enrollees. We find that visits among Medicaid enrollees in state-years where a copayment is in place are significantly less likely to be for nonurgent reasons. Our findings suggest that copayments may be an effective tool for reducing use of the ED for nonurgent care.


A comparison of electronic and manual dynamometry and goniometry in patients with fracture of the distal radius and healthy participants.
The purpose of this study was to assess the intra-rater and inter-rater reliability of electronic and manual dynamometry and goniometry in healthy volunteers, and the inter-instrument reliability in the assessment of healthy volunteers and patients recovering after a fracture of the distal radius. Grip strength, grip fatigue, pinch strength and range of motion were assessed in all participants with both the manual and electronic instruments by two physiotherapists and orthopaedic specialist trainee. The measures of dynamometry demonstrated excellent reliability (intra-class correlation coefficient >0.90), with the instruments found to be interchangeable with the exception of the grip fatigue. Variable intra-rater and inter-rater reliability was demonstrated with all planes of movement for the goniometry measures regardless of the instrument used. The results of this study support the continued use of dynamometry in the clinical setting, but raise questions regarding the use of goniometry measurements. Diagnostic level III.


A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-aza 2'-deoxycytidine.
Epigenetic mechanisms, such as DNA methylation and histone deacetylation, may play a role in loss of estrogen receptor alpha (ER) expression in ER negative human breast cancer cells. Our previous studies showed that pharmacologic inhibition of these mechanisms using the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (AZA), and the histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), resulted in expression of functional ER mRNA and protein. Therefore, we sought to characterize the effects of a recently described HDAC inhibitor, Scriptaid, on cell growth and ER expression and function in ER negative human breast cancer cell lines. Scriptaid treatment of three ER negative cell lines, MDA-MB-231, MDA-MB-435 and Hs578t, resulted in significant growth inhibition and increased acetylation of H3 and H4 histone tails. Quantitative Real Time PCR showed 2000-20,000-fold increase of ER mRNA transcript in all three cell lines after 48 h of Scriptaid treatment. Further, dose dependent re-expression of an estrogen responsive gene, the progesterone receptor (PR), indicated that induced ER is functional. As seen with TSA and AZA, Scriptaid and AZA co-treatment was more effective in inducing ER than Scriptaid or AZA alone. In vivo analysis using a xenograft mouse model bearing MDA-MB-231 tumors showed decreased tumor growth following Scriptaid or TSA treatment. Our results indicate that the novel HDAC inhibitor, Scriptaid, inhibits tumor growth in vitro and in vivo and, in conjunction with AZA, acts to re-express functional ER. These data suggest that Scriptaid or related HDAC inhibitors are candidates for further study in breast cancer.


Point-of-Care Estimated Radiation Exposure and Imaging Guidelines Can Reduce Pediatric Radiation Burden.
The steady increase in the use of computed tomography (CT) has particular concerns for children. Family physicians must often select pediatric imaging without any decision support. We hypothesized that point-of-care decision support would lead to the selection of imaging that lowered radiation exposure and improved guideline congruence. Our double-blind, randomized simulation included family physicians in the Military Health System. Participants initially reviewed a pediatric hematuria scenario and selected imaging without decision support. Participants were subsequently randomized to either receive imaging-appropriateness guidelines and then estimated radiation exposure information or receive estimated radiation information then guidelines; imaging selections were required after each step. The primary outcome was the selected imaging modality with point-of-care decision support. The first arm increased CT ordering after viewing the guidelines (P = .008) but then decreased it after reviewing radiation exposure information (P = .007). In the second arm radiation information decreased CT and plain film use (P = not significant), with a subsequent increase in ultrasound and CT after the guideline presentation (P = .05). Decision support during a simulated pediatric scenario helped family physicians select imaging that lowered radiation exposure and was aligned with current guidelines, especially when presented with radiation information after guideline review. This information could help inform electronic medical record design.


Coupling between 3D displacements and rotations at the glenohumeral joint during dynamic tasks in healthy participants.
Glenohumeral displacements assessment would help to design shoulder prostheses with physiological arthrokinematics and to establish more biofidelic musculoskeletal models. Though displacements were documented during static tasks, there is little information on their 3D coupling with glenohumeral angle during dynamic tasks. Our objective was to characterize the 3D glenohumeral displacement-rotation couplings during dynamic arm elevations and rotations. Glenohumeral displacements were measured from trajectories of reflective markers fitted on intracortical pins inserted into the scapula and humerus. Bone geometry was recorded using CT-scan. Only four participants were recruited to the experiment due to its invasiveness. Participants performed dynamic arm abduction, flexion and axial rotations. Linear regressions were performed between glenohumeral displacements and rotations. The pin of the scapula of one participant moved, his data were removed from analysis, and results are based on three participants. The measurement error of glenohumeral kinematics was less than 0.15mm and 0.2°. Maximum glenohumeral displacements were measured along the longitudinal direction and reached up to +12.4mm for one participant. Significant couplings were reported especially between longitudinal displacement and rotation in abduction (adjusted R(2) up to 0.94). The proposed method provides the potential to investigate glenohumeral kinematics during all kinds of movements. A linear increase of upward displacement during dynamic arm elevation was measured, which contrasts with results based on a series of static poses. The systematic investigation of glenohumeral displacements under dynamic condition may help to provide relevant recommendation for the design of shoulder prosthetic components and musculoskeletal models.


Characterization of sustained [Ca2+]i increase in pancreatic acinar cells and its relation to amylase secretion.
The sustained increase in cytosolic free Ca2+ concentration ([Ca2+]i) during maximal stimulation of rat pancreatic acini with carbamylcholine (10(-5) M) was investigated in individual acinar cells by microspectrofluorometric analysis of fura-2. After the large initial [Ca2+]i increase from intracellular stores, [Ca2+]i remained significantly elevated as long as the stimulus was applied. The amplitude of this plateau was dependent on the median Ca2+ concentration ([Ca2+]o) being 45-50 nM above prestimulation in medium with 1 mM [Ca2+]o increasing to 90 nM at 10 mM [Ca2+]o. This Ca2+ plateau was completely blocked by 2.5 mM Ni2+ and 0.25 mM La3+ but was unaffected by elevated K+ or the Ca2+ channel blocker D 600. Mn2+ was able to enter the cytosol after the cell stimulation as indicated by intracellular quenching of fura-2, indicating that acinar cells possess a Mn2(+)-permeable Ca2+ channel. Elimination of [Ca2+]o or addition of Ni2+ and Mn2+ to the medium reduced the level of sustained amylase secretion in a reversible manner under superfusion conditions. Increasing [Ca2+]i above the normal level by increasing [Ca2+]o had no effect on amylase secretion. The process for sustained Ca2+ entry was pH sensitive; decreasing extracellular pH (pHo) to 6.5-6.8 during the cell stimulation resulted in a reduction of the sustained [Ca2+]i plateau level and a decrease in sustained amylase secretion. By contrast, increasing pHo to 8.0 enhanced the level of the sustained [Ca2+]i in a Ni2(+)-sensitive manner but did not increase amylase release. Changes in cytosolic pH had only minimal effects on the sustained [Ca2+]i plateau. The results demonstrate a receptor-mediated Ca2+ entry mechanism, which results in a small increase in [Ca2+]i important in the maintenance of sustained amylase release.


Are Immigrant-Origin Candidates Penalized Due to Ingroup Favoritism or Outgroup Hostility?
An influential explanation for the persistent political underrepresentation of minorities in elected office is that minority candidates are discriminated against by voters of the dominant ethnic group. We argue, however, for the need to distinguish between two forms of discrimination: ingroup favoritism and outgroup hostility. We measure the impact of each by using an extensive data set drawn from Swiss elections, where voters can cast both positive and negative preference votes for candidates. Our results show that immigrant-origin candidates with non-Swiss names incur an electoral disadvantage because they receive more negative preference votes than candidates with typically Swiss names. But we also find that minority candidates face a second disadvantage: voters discriminate in favor of majority candidates by allocating them more positive preference votes. These two forms of electoral discrimination are critically related to a candidate's party, whereas the impact of the specific outgroup to which a minority candidate belongs is less pronounced than expected.


[Rehabilitative elements for the treatment of patients with mental disorders: are they considered in the development of guidelines?].
In the context of the current discussion of integrating rehabilitative elements into the (acute) treatment of patients with mental disorders, it is investigated what rehabilitative elements actually are and whether these elements are considered in existing guidelines. An expert-based consensus, especially results of expert ratings using a 46-item questionnaire (Delphi Technique; n = 16), shows that it is possible to specify rehabilitative elements, although there are still aspects which need further clarification. Analyses of current guidelines (using published guidelines for panic disorders) demonstrate that rehabilitative elements which are rated as important by the experts are only marginally mentioned in guidelines up to now. A considerable need for research exists for a further specification of rehabilitative elements and for the development of evidence based recommendations in the form of guidelines.


Endovascular approaches for traumatic arterial lesions.
Vascular injuries caused by blunt or penetrating trauma can be challenging to diagnose and treat, particularly when they involve central vessels. Endovascular treatment for vascular trauma includes the placement of embolization coils and intravascular stents and the employment of stented grafts. The use of stented grafts appears to be associated with decreased blood loss, a less invasive insertion procedure, reduced requirements for anesthesia, and a limited need for an extensive dissection in a traumatized field. These advantages are especially important in patients with central arteriovenous fistulas or false aneurysms, particularly those who are critically ill from other coexisting injuries or medical comorbidities. In these circumstances, the use of stented grafts already appears justified to treat traumatic central arterial lesions. Endovascular grafts are important tools for the treatment of vascular trauma, and they should be included in the armamentarium of the vascular surgeon.


Multimode imaging in the thermal infrared for chemical contrast enhancement. Part 2: Simulation driven design.
We present a simulation-driven process to design an infrared camera system that is tuned to specific analytes of interest based on "molecular factor computing". There are many factors involved in optimizing discrimination using optical filtering aids, including, but not limited to, the detector response, optical throughput of the system, optical properties of the samples, and optical properties of the materials for sensitizing films/filters. There are nearly infinite possible setups for the system, which means it is neither cost nor time efficient to physically test each one. In lieu of this, we developed routines in MATLAB (The Mathworks, Natick, MA) that simulate the camera output, per pixel, given specific conditions. Beginning with measured spectra of calibration samples or standards and using an objective function or figure of merit (FOM) to measure simulated performance, these routines evaluate large numbers of combinations of chemical films as filters for discrimination based on linear discriminant analysis (LDA). In this study, the FOM was the Fisher ratio between a neat fabric and one stained with either a polymer film or blood.


Age-related differences in functional brain network segregation are consistent with a cascade of cerebrovascular, structural, and cognitive effects.
Age-related declines in cognition are associated with widespread structural and functional brain changes, including changes in resting-state functional connectivity and gray and white matter status. Recently we have shown that the elasticity of cerebral arteries also explains some of the variance in cognitive and brain health in aging. Here, we investigated how network segregation, cerebral arterial elasticity (measured with pulse-DOT-the arterial pulse based on diffuse optical tomography) and gray and white matter status jointly account for age-related differences in cognitive performance. We hypothesized that at least some of the variance in brain and cognitive aging is linked to reduced cerebrovascular elasticity, leading to increased cortical atrophy and white matter abnormalities, which, in turn, are linked to reduced network segregation and decreases in cognitive performance. Pairwise comparisons between these variables are consistent with an exploratory hierarchical model linking them, especially when focusing on association network segregation (compared with segregation in sensorimotor networks). These findings suggest that preventing or slowing age-related changes in one or more of these factors may induce a neurophysiological cascade beneficial for preserving cognition in aging.


Perinatel outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis.
To determine whether the incidence of adverse obstetric outcomes is higher in singleton pregnancies achieved by in vitro fertilization (IVF) than in spontaneously conceived singletons matched for maternal age. We used comprehensive search strategies to search MEDLINE and EMBASE databases. We selected case-control and cohort studies that compared singleton pregnancies conceived by IVF or intracytoplasmic sperm injection (ICSI) with spontaneously conceived singletons (matched for maternal age [case-control studies] or controlled for maternal age [cohort studies]). Two reviewers independently assessed titles, abstracts, and study quality and extracted data. Statistical analysis was performed with Review Manager for Windows (Version 4.2, Oxford, UK). We performed meta-analysis of dichotomous data, using odds ratios (ORs) as measures of effect size, with a random effects model. We followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines for meta-analysis of observational studies. Singleton pregnancies resulting from IVF have increased rates of poor obstetric outcome, compared with spontaneously conceived singletons matched for maternal age, with increases in perinatal mortality (OR 2.40; 95% confidence interval [CI] 1.59-3.63), preterm birth at < 33 weeks' gestation (OR 2.99; 95% CI 1.54-5.80), preterm birth at < 37 weeks' gestation (OR 1.93; 95% CI 1.36-2.74), very low birth weight (< 1500 g) (OR 3.78; 95% CI 4.29-5.75), small for gestational age (OR 1.59; 95% CI 1.20-2.11), and congenital malformations (OR 1.41; CI 1.06-1.88). IVF singleton pregnancies have increased rates of poor obstetric outcome, compared with spontaneously conceived singletons matched for maternal age.


Sucralfate in the prevention of radiation-induced oral mucositis.
Radiotherapy-induced mucositis decreases the quality of life by impairing eating, swallowing, and talking and by disturbing sleep. Mucositis may also predispose to local and systemic infections and may cause interruption of radiotherapy course. We studied the efficacy of sucralfate suspension in the prevention and management of oral mucositis and pain during radiotherapy in a double-blind, placebo-controlled, randomized, prospective trial. Twenty-eight patients with head and neck cancer were included in the study. The patients were randomized to use either sucralfate mouth washing (n = 18) or placebo washing (n = 10) during irradiation. Oral mucositis and symptoms were assessed by the same physician using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. All patients developed varying degrees of radiation-induced mucositis. Grade 4 mucositis was not encountered in any patient. One patient had grade 1, seven patients grade 2, and two patients grade 3 mucositis in placebo group. In sucralfate group, nine patients each had grade 1 and grade 2 with no grade 3 mucositis. Patients in the sucralfate group experienced significantly lower degree of mucositis than placebo group (p < 0.05). Sucralfate mouth washing is beneficial in decreasing the intensity of radiation-induced mucositis and oral discomfort. It is cheap, easy to administer with no serious side effect, and may be routinely used in patients receiving head and neck radiotherapy.


Children born in the summer have increased risk for coeliac disease.
Coeliac disease, also called permanent gluten sensitive enteropathy, is being recognised as a widespread health problem. Defining the possible role of environmental factors in its aetiology might open doors to primary prevention. This study therefore analysed if the risk for coeliac disease varies with month of birth as a proxy for a seasonal pattern for possible causal environmental exposure(s). A population based incidence register of coeliac disease in children below 15 years of age covering the period from 1973 to 1997. Incidence rates were calculated by month of birth, stratified for age at diagnosis. Poisson regression analyses were used to estimate the relative risk for coeliac disease for children below 2 years of age by season of birth, also taking into account gender and time period of diagnosis. Sweden. All 2151 children in the study base with verified coeliac disease. The risk for coeliac disease was significantly higher if born during the summer as compared with the winter (RR=1.4, 95% CI 1.2 to 1.7), but only in children below 2 years of age at diagnosis. This relative seasonal risk pattern prevailed during a 10 year epidemic of coeliac disease, although incidence rates varied threefold. The incidence was constantly higher among girls as compared with boys, but boys showed a more pronounced seasonal variation in risk than girls. An increased coeliac disease risk in children born in the summer compared with the winter reflects causal environmental exposure(s) with a seasonal pattern. Infections might be the exposure of importance, either by means of a direct causal role and/or through interaction with other exposures, for example, gluten intake. However, non-infectious exposures should also be explored as possible contributing causal factors.


Advanced Magnetic Resonance Imaging Techniques in Tuberculous Meningitis.
Tuberculous meningitis (TBM) is a highly devastating manifestation of tuberculosis. So far, the major role of the neuroradiology in the management of TBM has been restricted to diagnosis and follow-up of the complications. This study aimed to establish the use of advanced magnetic resonance imaging (MRI) techniques in the early detection of sequelae of TBM like vasculitis and hydrocephalous. In this prospective observational study, 30 patients of TBM were recruited during 1 year at a tertiary care health center of northern India and their serial MRI brain was done. Patients were between 18 and 45 years of age. Basal/Sylvian exudates were seen in 90% of patients, hydrocephalus was found in 30% of patients and infarcts were found in 27% of patients. No significant difference was found between the mean, mean diffusivity (MD), and mean fractional anisotropy (FA) in frontal white matter, basal ganglia, thalamus, pons of cases and controls. A significant difference was seen between mean cerebral blood flow (CBF) in the region of basal ganglia of cases and controls (P < 0.05). No significant difference was seen between mean CBF in frontal white matter, thalamus of cases and controls. Diffusion tensor imaging parameters, MD, and FA were abnormal in the region of infarcts (basal ganglia) in three patients in the first scan, the parameters normalized in one patient (late subacute to chronic infarct in the first scan), and they remained abnormal in two patients. Advanced MRI techniques (magnetization transfer imaging) is helpful in visualizing hyperintense thickened meninges in basal cisterns and Sylvian fissures on pre-contrast imaging, and in identifying reduced CBF in the region of basal ganglia.


Blockwise processing applied to brain microvascular network study.
The study of cerebral microvascular networks requires high-resolution images. However, to obtain statistically relevant results, a large area of the brain (several square millimeters) must be analyzed. This leads us to consider huge images, too large to be loaded and processed at once in the memory of a standard computer. To consider a large area, a compact representation of the vessels is required. The medial axis is the preferred tool for this application. To extract it, a dedicated skeletonization algorithm is proposed. Numerous approaches already exist which focus on computational efficiency. However, they all implicitly assume that the image can be completely processed in the computer memory, which is not realistic with the large images considered here. We present in this paper a skeletonization algorithm that processes data locally (in subimages) while preserving global properties (i.e., homotopy). We then show some results obtained on a mosaic of three-dimensional images acquired by confocal microscopy.


Clinicopathological analysis of central and extraventricular neurocytoma: a report of 17 cases.
Neurocytoma, a rare brain tumor, is characterized by a mass located mainly in cerebral ventricles. It is prone to be misdiagnosed as oligodendroglioma or ependymoma due to their similar histopathological features in clinical practice. This study aimed to examine the clinicopathological features and differential diagnosis of central and extraventricular neurocytoma. The clinical and histopathological data of 17 patients (male: female=7:10; age: 4-41 years; mean age: 27.4 years) with central or extraventricular neurocytoma were retrospectively analyzed. These patients showed typical radiological, histopathological and immunohistochemical features of neurocytoma. The tumor tissue was found to be composed of small uniform cells with round nuclei and clear cytoplasm resembling that of oligodendroglioma and ependymoma. Immunohistochemistry revealed the tumor tissues were positive for neuronal markers such as synaptophysin (SYN) and neuronal nuclear antigen (NeuN). It was concluded histopathological features of neurocytoma overlaps with some tumors in the central neural system. Immunopositivity for SYN and NeuN can help differentially diagnose neurocytoma.


Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats.
Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic effects of BAs. Here we show that rats fed a diet containing saithe fish protein hydrolysate (saithe FPH), rich in taurine and glycine, for 26 days had markedly elevated fasting plasma BA levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal/retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism.


On a method of binary-picture representation and its application to data compression.
A method of representing a binary pictorial pattern is developed. Its original idea comes from a sequence of terminal symbols of a context-free grammar. It is a promising technique of data compression for ordinary binary-valued pictures such as texts, documents, charts, etc. Fundamental notions like complexity, primitives, simplifications, and other items about binary-valued pictures are introduced at the beginning. A simple context-free grammar G is also introduced. It is shown that every binary-valued picture is interpretable as a terminal sequence of that G. The DF-expression is defined as the reduced terminal sequence of G. It represents the original picture in every detail and contains no surplus data for reproducing it. A quantitative discussion about the total data of a DF-expression leads to the conclusion that any binary-valued picture with complexity less than 0.47 is expressed by the DF-expression with fewer data than the original ones. The coding algorithm of original data into the DF-expression is developed. It is very simple and recursively executable. Experiments were carried out using a PDS (photo digitizing system), where test pictures were texts, charts, diagrams, etc. with 20 cm × 20 cm size. Data compression techniques in facsimile were also simulated on the same test pictures. Throughout these studies it was made clear that the DF-expression is a very effective technique as a data compression for binary pictorial patterns not only because it yields high data compression but also because its coding and decoding algorithms are very feasible.


Refitted inclined plate for improving suspended solids removal in standard storm-water sumps.
Suspended solids (SS) in the storm-water makes up a significant source of total suspended solids in wet weather flow. With appropriate modification and maintenance, the standard sumps in the drainage system can remove SS from storm-water runoff as a best management practice device. To increase the removal efficiency, especially in the condition of high flow rate, inclined plates, based on the shallow pool sedimentation theory, have been designed and refitted to the sump. Its performance under the different surface load and flow rate were evaluated through scale models. The results show that the preliminary design, Model A, had limited removal efficiency, and even played a negative role sometimes due to the concentrated flow in the axis. The optimizations through installing a non-uniform porous baffle (Model B) and adopting inverted V-shaped plates (Model C) were improved, and results show that removal efficiency rate can be increased by around 15-20%, even at high flow rates. Moreover, too many plates cannot improve the removal rate further, because they make the cross-section decline and lead to higher velocity between plates.


Angiogenesis in health and disease.
Blood vessels constitute the first organ in the embryo and form the largest network in our body but, sadly, are also often deadly. When dysregulated, the formation of new blood vessels contributes to numerous malignant, ischemic, inflammatory, infectious and immune disorders. Molecular insights into these processes are being generated at a rapidly increasing pace, offering new therapeutic opportunities that are currently being evaluated.


The border community and immigration stress scale: a preliminary examination of a community responsive measure in two Southwest samples.
Understanding contemporary socio-cultural stressors may assist educational, clinical and policy-level health promotion efforts. This study presents descriptive findings on a new measure, the border community and immigration stress scale. The data were from two community surveys as part of community based participatory projects conducted in the Southwestern US border region. This scale includes stressful experiences reflected in extant measures, with new items reflecting heightened local migration pressures and health care barriers. Stressors representing each main domain, including novel ones, were reported with frequency and at high intensity in the predominantly Mexican-descent samples. Total stress was also significantly associated with mental and physical health indicators. The study suggests particularly high health burdens tied to the experience of stressors in the US border region. Further, many of the stressors are also likely relevant for other communities within developed nations also experiencing high levels of migration.


Nevirapine clearance from plasma in African adults stopping therapy: a pharmacokinetic substudy.
To measure nevirapine elimination in African adults undertaking a structured treatment interruption (STI) in the DART trial. Cohort (16 women, 5 men; median weight 61 kg) within a randomized trial of management strategies. Plasma nevirapine was measured by validated high performance liquid chromatography at 0,1,2,3 and 4 weeks after stopping the drug in a subset of patients undertaking an STI. All patients continued lamivudine plus zidovudine/stavudine for a further 7 days. Two patients with no or low plasma nevirapine concentration at baseline were excluded. Geometric mean plasma concentration when nevirapine was stopped in the remaining 19 patients was 6421 ng/ml (range, 3724-9473). Nevirapine was detected in 15/18 (83%) patients at 1 week, and 5/19 (26%) patients at 2 weeks but was not found any samples collected after 2 weeks. Only one patient had > 100 ng/ml (limit of quantification) at 2 weeks (415 ng/ml, female). The median times to reach thresholds of 200, 100 and 20 ng/ml (limit of detection) were estimated to be 7.6 [interquartile range (IQR), 7.0-10.1], 9.3 (IQR, 8.7-13.0) and 13.2 (IQR, 12.3-18.4) days, respectively, with 3/19 (16%) and 14/19 (74%) estimated to have reached < 20 ng/ml by 7 and 14 days, respectively. Although elimination of nevirapine was faster than previously published after a single dose, the data suggest that an additional staggered period of 7-10 days with dual nucleotide reverse transcriptase inhibitor cover is necessary for African patients discontinuing nevirapine.


Continuous postoperative pericardial flushing reduces postoperative bleeding after coronary artery bypass grafting: A randomized trial.
Prolonged or excessive bleeding after cardiac surgery can lead to a broad spectrum of secondary complications. One of the underlying causes is incomplete wound drainage, with subsequent accumulation of blood and clots in the pericardium. We developed the continuous postoperative pericardial flushing (CPPF) therapy to improve wound drainage and reduce postoperative blood loss and bleeding-related complications after cardiac surgery. This study compared CPPF to standard care in patients after coronary artery bypass grafting (CABG). This is a single center, open label, randomized trial that enrolled patients at the Amsterdam UMC, location AMC, Amsterdam, the Netherlands. The study was registered at the 'Netherlands Trial Register', study identifier NTR5200 [1]. Adults undergoing CABG were randomly assigned to receive CPPF therapy or standard care, participants and investigators were not masked to group assignment. The primary end point was postoperative blood loss in the first 12-hours after surgery. Between the January 15, 2014 and the March 13, 2017, 169 patients were enrolled and assigned to CPPF therapy (study group; n = 83) or standard care (control group; n = 86). CPPF reduced postoperative blood loss when compared to standard care (median differences -385 ml, reduction 76% p=≤0.001), with the remark that these results are overestimated due to a measurement error in part of the study group. None of patients in the study group required reoperation for non-surgical bleeding versus 3 (4%, 95% CI -0.4% to 7.0%) in the control group. None of the patients in the study group suffered from cardiac tamponade, versus 3 (4%, 95% CI -0,4% to 7.0%) in the control group. The incremental cost-effectiveness ratio was €116.513 (95% bootstrap CI €-882.068 to €+897.278). The use of CPPF therapy after CABG seems to reduce bleeding and bleeding related complications. With comparable costs and no improvement in Qualty of Life (QoL), cost consideration for the implementation of CPPF is not relevant. None of the patients in the study group required re-interventions for non-surgical bleeding or acute cardiac tamponade, which underlines the proof of concept of this novel therapy. This study was funded by ZonMw, the Netherlands organization for health research and development (project 837001405).


Birthweight of babies born to migrant mothers - What role do integration policies play?
Birthweights of babies born to migrant women are generally lower than those of babies born to native-born women. Favourable integration policies may improve migrants' living conditions and contribute to higher birthweights. We aimed to explore associations between integration policies, captured by the Migrant Integration Policy Index (MIPEX), with offspring birthweight among migrants from various world regions. In this cross-country study we pooled 31 million term birth records between 1998 and 2014 from ten high-income countries: Australia, Belgium, Canada, Denmark, Finland, Japan, Norway, Spain, Sweden and United Kingdom (Scotland). Birthweight differences in grams (g) were analysed with regression analysis for aggregate data and random effects models. Proportion of births to migrant women varied from 2% in Japan to 28% in Australia. The MIPEX score was not associated with birthweight in most migrant groups, but was positively associated among native-born (mean birthweight difference associated with a 10-unit increase in MIPEX: 105 g; 95% CI: 24, 186). Birthweight among migrants was highest in the Nordic countries and lowest in Japan and Belgium. Migrants from a given origin had heavier newborns in countries where the mean birthweight of native-born was higher and vice versa. Mean birthweight differences between migrants from the same origin and the native-born varied substantially across destinations (70 g-285 g). Birthweight among migrants does not correlate with MIPEX scores. However, birthweight of migrant groups aligned better with that of the native-born in destination counties. Further studies may clarify which broader social policies support migrant women and have impacts on perinatal outcomes.


Risk factors for recurrence of paranasal sinus mucoceles after ESS.
Paranasal sinus mucoceles are benign, expansive processes filled with mucus and bordered by respiratory mucosa. The purpose of our study was to determine risk factors for recurrence of mucoceles after endoscopic sinus surgery (ESS) based on clinical and radiological characteristics. We performed a retrospective review of 57 patients consecutively treated endoscopically for mucoceles between 1992 and 2002 at the UZ Leuven, a tertiary referral university hospital. Paranasal sinus mucoceles predominantly occurred in the maxillary sinus and the fronto-ethmoidal region (both 35%). In 69% of patients there was a history of sinus surgery (51%) or facial trauma (18%). Recurrence occurred in 5 of 49 patients who were treated by ESS in elective circumstances, while four of eight patients who underwent ESS at the moment of acute infection had recurrence (p = 0.004). Although all recurrences following elective ESS occurred in mucoceles related to previous facial trauma or sinus surgery, this relationship was not statistically significant (p = 0.2). In three patients, significant extension outside the sinus wall was present; three other patients had multiple mucoceles. Presence of multiple mucoceles and significant extension outside the sinus walls were also risk factors for recurrence (p = 0.002 and p = 0.001, respectively). In one patient with recurrence, the frontal recess was damaged during previous ESS. Three conditions can be considered risk factors for mucocele recurrence after ESS: surgery at a moment of acute infection, presence of multiple mucoceles, and significant extension outside the sinus wall.


Examining non-racial segregation: a micro-ecological approach.
A number of studies in both South Africa and the United States of America have indicated the presence of an 'informal' segregation that is active in everyday life spaces and which is resistant to changes in macro level social policy. This research has however been conducted in societies where segregation and division has been based on skin colour. We sought to adapt a micro-ecological technique for use in a non-racially segregated setting, in this case lecture theatres at a University in Northern Ireland. Using seat numbers to examine seating patterns we found that levels of segregation persisted throughout a semester. The success of this methodology in capturing this information has far-reaching implications for the future study of the micro-ecology of contact.


Circulating biomarkers of iron storage and clearance of incident human papillomavirus infection.
Iron is an essential mineral for both cellular and pathogen survival and is essential for viral replication. In turn, iron metabolism has been shown to be altered by several viral infections. However, little is known about the association between iron status and human papillomavirus (HPV) natural history. We hypothesize iron to be an HPV cofactor that is associated with longer duration of infection. Ferritin and soluble transferrin receptor (sTfR) were measured in baseline serum samples from 327 women enrolled in the Ludwig-McGill cohort. Incident HPV clearance rates (any-type, oncogenic HPV, nononcogenic HPV, and HPV-16) over a 3 year time period were estimated from Cox proportional hazard models accounting for correlations between multiple infections. Women with ferritin levels above the median were less likely to clear incident oncogenic HPV [adjusted hazard ratio (AHR), 0.73; 95% confidence interval (CI), 0.55-0.96] and HPV-16 infections (AHR, 0.29; 95% CI, 0.11-0.73). Using physiologic cutoff points, women with enriched iron stores (>120 μg/L) were less likely to clear incident oncogenic HPV infections than those with low levels of iron (<20 μg/L; AHR, 0.34; 95% CI, 0.15-0.81). This study observed that women with the highest ferritin levels were less likely to clear incident oncogenic and HPV-16 infections than women with low ferritin. Rising iron stores may decrease probability of clearing new HPV infection, possibly by promoting viral activity and contributing to oxidative DNA damage. This novel study suggests that elevated iron stores may put women at risk for persistent HPV infection, an early event in cervical carcinogenesis. Further examination of the association between iron status and HPV natural history is warranted.


Allergens in household dust and serological indicators of atopy and sensitization in Detroit children with history-based evidence of asthma.
Home exposure to allergens is an important factor in the development of sensitization and subsequent exacerbations of allergic asthma. We investigated linkages among allergen exposure, immunological measurements, and asthma by examining (1) reservoir dust allergen levels in homes, (2) associations between presence of allergens in homes and sensitization status of resident children, and (3) associations between asthma status and total IgE, atopy (by Phadiatop), and positive allergen-specific tests. The study protocol was approved by Institutional Review Boards (IRBs) of the University of North Carolina Chapel Hill; Westat, Inc.; and the US Environmental Protection Agency Human Research Protocol Office. Data were collected from questionnaires, serum analyses, and household vacuum dust. Children (n = 205) were predominately African American (AA) (85.4%) and 51.6% were asthmatic. Sera from 185 children and home dust samples (n = 141) were analyzed for total and specific IgE antibodies to allergens from cat and dog dander, cockroach, dust mites, mice, rats, and molds. Sixty percent of the homes had detectable levels of three or more dust allergens. The proportions of children with positive allergen-specific IgE tests were dust mite (32%), dog (28%), cat (23%), cockroach (18%), mouse (5%), rat (4%), and molds (24-36%). Children testing positive to a single allergen also had positive responses to other allergens. Those children with positive serum tests for cat, dog, and dust mite lived in homes with detectable levels of cat (51%), dog (90%), and dust mite (Der f 1) (92%) allergens. Correlations between children's specific IgE levels and dust levels were linearly related for dog (p < .04), but not for cat (p = .12) or dust mite (Der f 1) (p = .21). Odds ratios (95% CI) for the associations between asthma and serum-specific IgE were over 1.0 for cat, dog, dust mite (Der f 1), cockroach, and four types of molds. House dust allergen exposure levels, however, exhibited no differences between asthmatic and non-asthmatic homes. Both the co-occurrence of multiple allergens in dust and the high frequency of multiple allergen sensitizations indicate that a broad-based intervention aimed at reducing multiple allergens (pets, pests, and molds) would be more successful than any approach that aimed at reducing one type of allergen.


Increased neurosteroid sensitivity--an explanation to symptoms associated with chronic work related stress in women?
Work related psychosocial stress can be accompanied by so called burnout syndrome with symptoms of mental exhaustion, physical fatigue, and cognitive dysfunction. Underlying mechanisms for acquiring burnout syndrome are not clear. Animal studies show that chronic stress is associated with altered release of GABA-A receptor modulating steroids (GAMS), altered composition of the GABA-A receptor and altered sensitivity to GAMS. In the present study we investigated if such changes occur in women with burnout syndrome. We further asked whether flumazenil (a benzodiazepine antagonist, but with positive modulating effects on GABA-A receptors with altered subunit composition) can block the effect of the GAMS allopregnanolone. Ten women with occupational psychosocial stress and burnout syndrome were compared with twelve healthy controls in an experimental setting. Saccadic eye velocity (SEV) was measured after an injection of allopregnanolone, followed by an injection of flumazenil and a second injection of allopregnanolone. The sensitivity to allopregnanolone was significantly higher in the patients compared to controls after the first injection (p=0.04) and the difference increased when the response per allopregnanolone concentration unit was compared (p=0.006). Following the flumazenil injection the burnout patients (p=0.016), but not controls, showed a decrease in SEV and flumazenil acted like a positive modulator that is agonistic. There was no significant difference between the groups after second allopregnanolone injection. In conclusion, patients with work related psychosocial stress and burnout syndrome show a different response to GABA-A receptor modulators than controls suggesting a changed GABA-A receptor function in these patients. More precisely we hypothesize that the α4 and delta subunits are up-regulated elevating the responsiveness to allopregnanolone and change the effect of flumazenil, which provides a potential explanation to the burnout syndrome. Flumazenil does not block the effect of allopregnanolone.


Immediate Effects of 3% Diquafosol and 0.1% Hyaluronic Acid Ophthalmic Solution on Tear Break-Up Time in Normal Human Eyes.
The purpose of this study was to evaluate the immediate effect of 3% diquafosol ophthalmic solution on tear break-up time (TBUT) in normal human eyes, and to compare it with that of saline and 0.1% hyaluronate ophthalmic solution. Cross sectional comparative study in the first study, 10 healthy volunteers underwent topical application of 2 different ophthalmic solutions in each eye. Saline was randomly applied to one eye and 3% diquafosol ophthalmic solution was added to the fellow eye. TBUT was measured and video recorded before application and at 5, 10, 15, and 20 min after. The TBUT in each eye was compared at each time point with regard to the 2 different ophthalmic solutions. In the second study, another 10 healthy volunteers were included. The same methods were used to compare the immediate effects of 0.1% hyaluronate and 3% diquafosol ophthalmic solution application on TBUT. In the first study, topical instillation of saline did not increase TBUT. However, 3% diquafosol significantly increased TBUT for up to 15 min after application. At every time point, the TBUT increased more significantly from baseline in the diquafosol group than it did in the saline group. In the second study, 0.1% hyaluronate increased TBUT for up to 5 min after application, while 3% diquafosol increased TBUT for up to 15 min. Although the TBUT changes after 5 min were not significantly different between the 2 groups, the TBUT changes at 10, 15, and 20 min were significantly greater in the 3% diquafosol group than they were in the 0.1% hyaluronic acid group (+1.58 ± 0.82 vs. +0.53 ± 1.36 at 10 min, +0.67 ± 0.91 vs. -0.04 ± 1.29 at 15 min, and -0.06 ± 0.96 vs. -0.59 ± 0.90, diquafosol group vs. hyaluronic acid group). One drop of 3% diquafosol increased TBUT for up to 15 min after application. The immediate effect of 3% diquafosol on TBUT was greater than that of saline and even that of 1% hyaluronate ophthalmic solution.


Congenital Diaphragmatic Hernia Defect Size and Infant Morbidity at Discharge.
Survival for infants with congenital diaphragmatic hernia (CDH) has gradually improved, yet substantial burden of disease remains. Although larger CDH defect sizes increase mortality, the association between defect size and morbidity has not been reported. Our objective was to evaluate the association of defect size with pulmonary, neurologic, and gastrointestinal morbidity at the time of hospital discharge. An international, prospective cohort study was performed. Patient demographics, intraoperative defect size, and clinical outcomes were reviewed. The primary outcome was morbidity at the time of discharge, which entailed supplemental oxygen requirement, abnormal neurologic clinical and radiographic findings, gastroesophageal reflux, supplemental nutrition, or pulmonary-, neurologic-, or gastrointestinal-related medications. A total of 3665 patients were included in the study cohort. Overall survival was 70.9%, and 84.0% of survivors were discharged from the hospital (16.0% transferred). Median age at discharge was 38 days (interquartile range [IQR] 23-69) and ranged from 22 (IQR 16-32) days for "A" (smallest) defects to 89 (IQR 64-132) days for "D" (largest) defects (P < .001). Of those discharged from the hospital, 1522 (74.2%) had pulmonary (n = 660, 30.2%), neurologic (n = 446, 20.4%), or gastrointestinal (n = 1348, 61.7%) morbidities, and multiple morbidities were diagnosed in 701 (34.7%) patients. On multivariable regression analyses incorporating key patient characteristics, defect size was consistently the greatest predictor of overall morbidity, hospital length of stay, and duration of ventilation. Infants with CDH are commonly discharged with ≥1 major morbidities. The size of the diaphragmatic defect appears to be the most reliable indicator of a patient's hospital course and discharge burden of disease.


Clinical study on evaluation of anti-cataract effect of Triphaladi Ghana Vati and Elaneer Kuzhambu Anjana in Timira (immature cataract).
Senile cataract is the leading cause of blindness according to the World Health Report, 1998. Till date no accepted medical treatment is available for cataract. In Ayurveda visual disturbances are described in the context of Timira, Kacha and Linganasha. Timira is an early stage characterized by blurring of vision and Linganasha is end stage where complete loss of vision occurs. Ancient scholars have advocated different Anjana application and oral medications in the Timira and Kacha stage. To study the efficacy of test drugs Triphaladi Ghana Vati and Elaneer Kuzhambu Anjana in immature cataract. In this trial patients having Senile Immature Cataract were randomized with equal probability to one of the two treatment Groups A and B (n = 20 each). In Group A Triphaladi Ghana Vati 500 mg internally for 3 months and in Group B Triphaladi Ghana Vati 500 mg internally and Elaneer Kuzhambu Anjana for local application were given. Assessment was done on the basis of blurring of vision, visualization of nonexisting things, difficulty in bright light and dim light or night vision, distant visual acuity, pinhole vision, best corrected visual acuity and cataract grading on slit lamp. Both groups showed statistically significant changes in blurring of vision, difficulty in glare, daytime and bright light, distant visual activity, pinhole vision, and best-corrected visual acuity. Group B also showed significant changes in difficulty in night time, visualization of nonexisting things and in nuclear cataract. The study establishes that test drugs can reduce and control the progress of immature cataract, and combined therapy was found more effective. Chakshushya Rasayana, early diagnosis and proper management on Doshic lines can prevent arrest or delay senile cataract.


Systemic effect comparisons of six inhaled corticosteroid preparations.
The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.


Soil bacterial community shifts after chitin enrichment: an integrative metagenomic approach.
Chitin is the second most produced biopolymer on Earth after cellulose. Chitin degrading enzymes are promising but untapped sources for developing novel industrial biocatalysts. Hidden amongst uncultivated micro-organisms, new bacterial enzymes can be discovered and exploited by metagenomic approaches through extensive cloning and screening. Enrichment is also a well-known strategy, as it allows selection of organisms adapted to feed on a specific compound. In this study, we investigated how the soil bacterial community responded to chitin enrichment in a microcosm experiment. An integrative metagenomic approach coupling phylochips and high throughput shotgun pyrosequencing was established in order to assess the taxonomical and functional changes in the soil bacterial community. Results indicate that chitin enrichment leads to an increase of Actinobacteria, γ-proteobacteria and β-proteobacteria suggesting specific selection of chitin degrading bacteria belonging to these classes. Part of enriched bacterial genera were not yet reported to be involved in chitin degradation, like the members from the Micrococcineae sub-order (Actinobacteria). An increase of the observed bacterial diversity was noticed, with detection of specific genera only in chitin treated conditions. The relative proportion of metagenomic sequences related to chitin degradation was significantly increased, even if it represents only a tiny fraction of the sequence diversity found in a soil metagenome.


New treatments for idiopathic thrombocytopenic purpura: rethinking old hypotheses.
The efficacy of thrombopoietin (TPO) mimetics in patients with idiopathic thrombocytopenic purpura (ITP) reaffirms that impaired platelet production is an important mechanism. New strategies to reduce platelet destruction, like rituximab, are also effective. To describe the efficacy and safety of rituximab and the TPO mimetics, romiplostim and eltrombopag, and how they relate to ITP pathogenesis. Narrative review summarizing full publications and meeting abstracts. A 4-week course of rituximab is associated with a platelet count response in 60% of patients with ITP, and durable responses have been observed. Subtle increases in infection have been reported. Romiplostim and eltrombopag are each associated with a 60 - 85% response while on treatment. Transient bone marrow reticulin with romiplostim and elevated liver enzymes with eltrombopag are rare side effects. The application of these agents in non-splenectomized patients requires further study.


Physiological demands of off-road vehicle riding.
The purpose of this study was to characterize the physiological demands of recreational off-road vehicle riding under typical riding conditions using habitual recreational off-road vehicle riders (n = 128). Comparisons of the physical demands of off-road vehicle riding were made between vehicle types (all-terrain vehicle (ATV) and off-road motorcycle (ORM)) to the demands of common recreational activities. Habitual riders (ATV = 56, ORM = 72) performed strength assessments before and after a representative trail ride (48 +/- 24.2 min), and ambulatory oxygen consumption was measured during one lap (24.2 +/- 11.8 min) of the ride. The mean VO2 requirement (mL x kg(-1) x min(-1)) while riding an off-road vehicle was 12.1 +/- 4.9 for ATV and 21.3 +/- 7.1 for ORM (P = 0.002), which is comparable to the VO2 required of many common recreational activities. Temporal analysis of activity intensity revealed approximately 14% of an ATV ride and 38% of an ORM ride are within the intensity range (940% VO2 reserve) required to achieve changes in aerobic fitness. Riding on a representative course also led to muscular fatigue, particularly in the upper body. On the basis of the measured metabolic demands, evidence of muscular strength requirements, and the associated caloric expenditures with off-road vehicle riding, this alternative form of activity conforms to the recommended physical activity guidelines and can be effective for achieving beneficial changes in health and fitness.


Hyperlactatemia and the Importance of Repeated Lactate Measurements in Critically Ill Patients.
The aim of the study was to describe the prevalence of hyperlactatemia and emphasis on repeated lactate measurements in critically ill patients, and the associated mortality. The study included 70 patients admitted in the Medical Intensive Care Unit at the Clinical Center, University of Sarajevo, in a 6-month period (July - December 2015). The following data were obtained: age, gender, reason for admission, Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation, lactate concentrations upon admission, after 24 and 48 hours, and outcome (discharge from hospital or death). Upon admission,hyperlactatemia was present in 91.4% patients with a mean concentration of lactate 4.13 ±1.21 mmol/L. Lactate concentration at 48 hours was independently associated within creased in-hospital mortality (P = 0.018). Persistent hyperlactatemia is associated with adverse outcome in critically ill patients. Lactate concentration at 48 hours is independently associated within creased in-hospital mortality and it represents a statistically significant predictive marker of fatal outcomes of patients. Blood lactate concentrations > 2.25 mmol/L should be used by clinicians to identify patients at higher risk of death.


Combined therapeutic hypothermia and barbiturate coma reduces interleukin-6 in the cerebrospinal fluid after aneurysmal subarachnoid hemorrhage.
Inflammatory response with cytokine release is reported to correlate with clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). In selected cases, hypothermia and barbiturate coma are applied as means for neuroprotection after severe SAH. Hypothermia and high-dose barbiturate are reported to attenuate the inflammatory response. In this pilot study, we assessed the effect of the combined therapy on the inflammatory response. In 15 patients with SAH, daily cerebrospinal fluid (CSF) and plasma samples were collected. Interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), IL-1beta, systemic leukocyte, and leukocyte counts in the CSF were quantified. Group 1 represented 7 cases treated with combined therapeutic hypothermia (33 degrees C) and barbiturate coma. Group 2 represented 8 cases without combined therapy. Compared with the systemic levels, all cases showed higher cytokine levels in the CSF. Mean IL-6 level in the CSF was significantly lower in group 1 (P<0.001). The ratio between IL-6 levels in the CSF and plasma, as a parameter for intrathecal synthesis, was significantly lower in group 1 (P=0.014). Mean CSF and systemic levels of TNF-alpha of group 1 were significantly higher compared with group 2 (P=0.009 and P<0.001). The mean systemic IL-1beta level was significantly lower in group 1 (P<0.001), as well as the leukocyte counts, both, systemic and in the CSF (P<0.001 and P=0.032). The present data show a most pronounced decrease of IL-6 levels in the CSF, beside decrease in systemic IL-1beta levels, systemic leukocyte counts, and CSF leukocyte counts in group 1, which would be expected to reflect an attenuation of inflammatory response. The impact and role of TNF-alpha remains unclear.


The effect of immersion on haemodynamic and fetal measures in uncomplicated pregnancies of nulliparous women.
To evaluate the effect of immersion in water on maternal haemodynamic measures and fetal heart rate patterns in healthy nulliparous women. A randomised cross-over study. Twenty pregnant women were studied between 26-29 weeks and between 34-37 weeks of gestation. The women were either immersed in water for 35 minutes or rested on a bed for a similar period of time. Maternal blood pressure, thoracic electrical bioimpedance, urine and blood samples, and fetal heart rate patterns were obtained before and after immersion or bedrest. Compared with bedrest and pre-immersion values, immersion resulted in a significant decrease in blood pressure, which returned to baseline values within 1.5 hour. Urine production increased for a short period after immersion, but 24 hour samples showed no difference compared with bedrest. Sodium, potassium and creatinine levels in urine remained constant. No significant changes were found for the other haemodynamic measures. There were no effects on fetal heart rate nor on its variation. In healthy pregnant women immersion for 35 minutes has a clear effect on blood pressure and urine production. However, these effects are short lasting.


Diverse immune environments in human lung tuberculosis granulomas assessed by quantitative multiplexed immunofluorescence.
The precise nature of the local immune responses in lung tuberculosis (TB) granulomas requires a comprehensive understanding of their environmental complexities. At its most basic level, a granuloma is a compact, organized immune aggregate of macrophages surrounded by myeloid, B and T cells. We established two complementary multiplex immunolabeling panels to simultaneously evaluate the myeloid and lymphocytic contexture of 14 human lung TB granulomas in formalin-fixed paraffin-embedded tissue samples. We observed diverse CD3+ and CD8+ T-cell and CD20+ B lymphocyte compositions of the granuloma immune environment and a relatively homogeneous distribution of all myeloid cells. We also found significant associations between CD8+ T-cell densities and the myeloid marker CD11b and phagocytic cell marker CD68. In addition, significantly more CD68+ macrophages and CD8+ T cells were found in Mycobacterium tuberculosis-infected granulomas, as detected by Ziehl-Neelsen staining. FOXP3 expression was predominately found in a small subset of CD4+ T cells in different granulomas. As the success or failure of each granuloma is determined by the immune response within that granuloma at a local and not a systemic level, we attempted to identify the presence of reactive T cells based on expression of the T-cell activation marker CD137 (4-1BB) and programmed cell death-1 (PD-1). Only a small fraction of the CD4+ and CD8+ T cells expressed PD-1. CD137 expression was found only in a very small fraction of the CD4+ T cells in two granulomas. Our results also showed that multinucleated giant cells showed strong PD-L1 but not CTLA-4 membrane staining. This study offers new insights into the heterogeneity of immune cell infiltration in lung TB granulomas, suggesting that each TB granuloma represents a unique immune environment that might be independently influenced by the local adaptive immune response, bacterial state, and overall host disease status.