Linking ground-water age and chemistry data along flow paths: implications for trends and transformations of nitrate and pesticides.
Tracer-based ground-water ages, along with the concentrations of pesticides, nitrogen species, and other redox-active constituents, were used to evaluate the trends and transformations of agricultural chemicals along flow paths in diverse hydrogeologic settings. A range of conditions affecting the transformation of nitrate and pesticides (e.g., thickness of unsaturated zone, redox conditions) was examined at study sites in Georgia, North Carolina, Wisconsin, and California. Deethylatrazine (DEA), a transformation product of atrazine, was typically present at concentrations higher than those of atrazine at study sites with thick unsaturated zones but not at sites with thin unsaturated zones. Furthermore, the fraction of atrazine plus DEA that was present as DEA did not increase as a function of ground-water age. These findings suggest that atrazine degradation occurs primarily in the unsaturated zone with little or no degradation in the saturated zone. Similar observations were also made for metolachlor and alachlor. The fraction of the initial nitrate concentration found as excess N2 (N2 derived from denitrification) increased with ground-water age only at the North Carolina site, where oxic conditions were generally limited to the top 5 m of saturated thickness. Historical trends in fluxes to ground water were evaluated by relating the times of recharge of ground-water samples, estimated using chlorofluorocarbon concentrations, with concentrations of the parent compound at the time of recharge, estimated by summing the molar concentrations of the parent compound and its transformation products in the age-dated sample. Using this approach, nitrate concentrations were estimated to have increased markedly from 1960 to the present at all study sites. Trends in concentrations of atrazine, metolachlor, alachlor, and their degradates were related to the timing of introduction and use of these compounds. Degradates, and to a lesser extent parent compounds, were detected in ground water dating back to the time these compounds were introduced.


Community surveillance of coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) Study: methods and initial two years' experience.
The community surveillance component of the Atherosclerosis Risk in Communities (ARIC) Study is designed to estimate patterns and trends of coronary heart disease (CHD) incidence, case fatality, and mortality in four U.S. communities. Community surveillance involves ongoing review of death certificates and hospital discharge records to identify CHD events in community residents aged 35-74 years. Interviews with next of kin and questionnaires completed by physicians and medical examiners or coroners were used to collect information on deaths, and review and abstraction of hospital records were used to collect information on possible fatal and nonfatal myocardial infarctions (MIs). Events were classified using standardized criteria. The initial 2-years' experience with case ascertainment and availability of information needed for classification of events is described. Average annual age-adjusted attack rates of definite MI and CHD mortality rates for blacks in two communities and whites in the four communities are presented and compared with rates based on unvalidated hospital discharge data and vital statistics. Age-adjusted rates based on ARIC classification of definite MI were lower than those based on hospital discharge diagnosis code 410 (e.g., 5.60/1000 and 11.50/1000 among Forsyth County white men, respectively). Age-adjusted rates of definite fatal CHD based on ARIC classification were similarly lower than rates based on underlying cause of death code 410; for example, Jackson black men had rates of 2.82/1000 and 4.52/1000 for definite fatal CHD and UCOD 410-414 or 429.2, respectively.


Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies.
The effect of interferon-beta1a (INF-beta1a; Rebif) was studied in patients with chronic motor neuropathies not improving after conventional treatments such as immunoglobulins, steroids, cyclophosphamide or plasma exchange. A prospective open study was performed with a duration of 6-12 months. Three patients with a multifocal motor neuropathy and one patient with a pure motor form of chronic inflammatory demyelinating polyneuropathy were enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of IBF-beta1a (6 MIU), three times a week. Primary outcome was assessed at the level of disability using the nine hole peg test, the 10 metres walking test, and the modified Rankin scale. Secondary outcome was measured at the impairment level using a slightly modified MRC sumscore. All patients showed a significant improvement on the modified MRC sumscore. The time required to walk 10 metres and to fulfil the nine hole peg test was also significantly reduced in the first 3 months in most patients. However, the translation of these results to functional improvement on the modified Rankin was only seen in two patients. There were no severe adverse events. Motor conduction blocks were partially restored in one patient only. Anti-GM1 antibody titres did not change. These findings indicate that severely affected patients with chronic motor neuropathies not responding to conventional therapies may improve when treated with INF-beta1a. From this study it is suggested that INF-beta1a should be administered in patients with chronic motor neuropathies for a period of up to 3 months before deciding to cease treatment. A controlled trial is necessary to confirm these findings.


Computational vaccinology and epitope vaccine design by immunoinformatics.
Human immune system includes variety of different cells and molecules correlating with other body systems. These instances complicate the analysis of the system; particularly in postgenomic era by introducing more amount of data, the complexity is increased and necessity of using computational approaches to process and interpret them is more tangible.Immunoinformatics as a subset of bioinformatics is a new approach with variety of tools and databases that facilitate analysis of enormous amount of immunologic data obtained from experimental researches. In addition to directing the insight regarding experiment selections, it helps new thesis design which was not feasible with conventional methods due to the complexity of data. Considering this features immunoinformatics appears to be one of the fields that accelerate the immunological research progression.In this study we discuss advances in genomics and vaccine design and their relevance to the development of effective vaccines furthermore several division of this field and available tools in each item are introduced.


Utility of the Roussel Uclaf Causality Assessment Method (RUCAM) to analyze the hepatic findings in a clinical trial program: evaluation of the direct thrombin inhibitor ximelagatran.
Causality assessment in drug-induced liver injury is often based on circumstantial evidence rather than a formal, systematic review. The Roussel Uclaf Causality Assessment Method (RUCAM) provides a more objective means of assessing causality of a suspected hepatotoxin but, to our knowledge, has never been used in the assessment of a single drug with unknown hepatotoxic potential in a clinical trial setting. We studied the utility of RUCAM in assessing the hepatic events during the long-term clinical trials of the oral direct thrombin inhibitor ximelagatran, which has been associated with an increased incidence of alanine aminotransferase (ALT) elevations. A total of 233 subjects with elevated ALT values signalling possibly severe hepatic injury were eligible for RUCAM analysis (198 ximelagatran and 35 comparator anticoagulants). RUCAM scores, calculated independently by the assessors, using the existing numerical criteria provided in its methodology, suggested a possible or probable causal relationship between ALT and ximelagatran in 37 and 27% of cases, respectively. Causality was excluded or unlikely in the remaining 36% of cases. However, in the course of utilizing RUCAM, several limitations to the methodology came to light, including awarding additional points for age > 55 years, an unspecified use of alcohol, and a latency period of < 90 days, which may have had the unintentional effect of raising the overall score. Moreover, rechallenge is highly rewarded by RUCAM but is seldom done in clinical practice or in clinical trials. We also found ambiguities in the extent to which other causes of liver injury were excluded, what constitutes a significant hepatotoxic concomitant medication, and whether a clinical trial drug should be considered as having an unknown hepatotoxic potential for purposes of RUCAM scoring. Increasing familiarity with the RUCAM over the course of the study allowed for only a slight improvement in concordance between and among the assessors regarding the scoring. While the results indicate that RUCAM can provide for an objective assessment of causality of the hepatotoxicity of a drug under development in the clinical trial setting, this study highlights a number of problems with the current scoring system that should be addressed by future enhancements of the methodology.


Induction of Antioxidant and Heat Shock Protein Responses During Torpor in the Gray Mouse Lemur, Microcebus murinus.
A natural tolerance of various environmental stresses is typically supported by various cytoprotective mechanisms that protect macromolecules and promote extended viability. Among these are antioxidant defenses that help to limit damage from reactive oxygen species and chaperones that help to minimize protein misfolding or unfolding under stress conditions. To understand the molecular mechanisms that act to protect cells during primate torpor, the present study characterizes antioxidant and heat shock protein (HSP) responses in various organs of control (aroused) and torpid gray mouse lemurs, Microcebus murinus. Protein expression of HSP70 and HSP90α was elevated to 1.26 and 1.49 fold, respectively, in brown adipose tissue during torpor as compared with control animals, whereas HSP60 in liver of torpid animals was 1.15 fold of that in control (P<0.05). Among antioxidant enzymes, protein levels of thioredoxin 1 were elevated to 2.19 fold in white adipose tissue during torpor, whereas Cu-Zn superoxide dismutase 1 levels rose to 1.1 fold in skeletal muscle (P<0.05). Additionally, total antioxidant capacity was increased to 1.6 fold in liver during torpor (P<0.05), while remaining unchanged in the five other tissues. Overall, our data suggest that antioxidant and HSP responses are modified in a tissue-specific manner during daily torpor in gray mouse lemurs. Furthermore, our data also show that cytoprotective strategies employed during primate torpor are distinct from the strategies in rodent hibernation as reported in previous studies.


[Assumption of sincerity in medicine].
Medical practice is always embedded in time and space, whatever its scientific and technical progress could claim as universal truths. The postulate of sincerity is one those contextual elements but it has become so pervasive that a gloss of evidence surrounds it. This situation is at risk of loosing its depth, as much as its limits. By bringing closer together sincerity with more usual notions (transparency, confidence, uncertainty), one could get more insight into these matters of concern in medical practice.


The efficacy of conservative treatment in patients with whiplash injury: a systematic review of clinical trials.
A systematic review of the literature. To assess the efficacy of conservative treatment in patients with whiplash injuries. Many treatments are available for patients with whiplash injury, but there continues to be no evidence for their accepted use. A computerized literature search of Medline, Embase, Cinahl, Psychlit, and the Cochrane Controlled Trial Register was performed. Studies were selected if the design was a (randomized) clinical trial; if all patients had sustained a whiplash injury; if the type of intervention was a conservative one; if pain, global perceived effect, and participation in daily activities were used as one of the outcome measures, and if the publication was written in English, French, German, or Dutch. The methodologic quality was independently assessed by two reviewers by using the Maastricht-Amsterdam list. Three quality scores were calculated using this criteria list: the Overall Methodologic Quality Score, the Internal Validity Score, and the Delphi Quality Score. The conclusion of the review was based on articles that scored a quality score of at least 50% of the maximum available score on two of three quality scores. Eleven studies met the inclusion criteria. Only three studies satisfied at least 50% on two of three ways of calculating a quality score, indicating overall poor methodology. There was a high rank correlation among the three ways of calculating a quality score. No statistical pooling was performed because of the heterogeneity of the interventions. This review indicates that active treatments show a beneficial long-term effect on at least one of the primary outcome measures. Caution is needed when drawing a valid conclusion on the efficacy of conservative treatments in patients with whiplash injury. It appears that "rest makes rusty," whereas active interventions have a tendency to be more effective in patients with whiplash injury.


Ergot Alkaloids in Fattening Chickens (Broilers): Toxic Effects and Carry over Depending on Dietary Fat Proportion and Supplementation with Non-Starch-Polysaccharide (NSP) Hydrolyzing Enzymes.
Ergot alkaloids (EA) are mycotoxins produced by Claviceps purpurea. EA-toxicity is poorly characterized for fattening chickens. Therefore, a dose-response study was performed to identify the lowest, and no observed adverse effect levels (LOAEL and NOAEL, respectively) based on several endpoints. Non-starch-polysaccharide (NSP) cleaving enzyme addition and dietary fat content were additionally considered as factors potentially influencing EA-toxicity. Feed intake was proven to respond most sensitively to the EA presence in the diets. This sensitivity appeared to be time-dependent. While LOAEL corresponded to a total dietary EA content of 5.7 mg/kg until Day 14 of age, it decreased to 2.03 mg/kg when birds were exposed for a period of 35 days. Consequently, NOAEL corresponded to an EA content of 2.49 mg/kg diet until Day 14 of age, while 1.94 mg/kg diet applied until Day 35 of age. Liver lesions indicating enzyme activities in serum were increased after 14 days of exposure. Dietary fat content and NSP-enzyme supplementation modified EA toxicity in an interactive manner. The EA residues in serum, bile, liver and breast meat were <5 ng/g suggesting a negligible carry over of intact EA.


The novel gene yvfI in Bacillus subtilis is essential for bacilysin biosynthesis.
Using transposon mutagenesis in Bacillus subtilis PY79, three independent mutants defective in production of bacilysin were isolated. To identify the genes in these mutant loci affecting bacilysin biosynthesis, the inserted transposon and its flanking regions were cloned and sequenced from each mutant. Transposon insertions in these three mutants were found to be in the yvfI gene which encodes an unknown protein similar to GntR family transcriptional regulators. For further confirmation, deletion mutants were constructed in which nucleotides 196-314 of the yvfI gene were removed. All resulting yvfI (Delta196-314)::spc deletion mutants exhibited bacilysin-negative phenotypes, as in the case of the yvfI::Tn10::spc insertional mutants. The lacR gene, encoding a transcriptional regulator, resides immediately downstream from the yvfI gene. Therefore, an insertion mutation was created in the lacR gene to demonstrate that the bacilysin negative phenotype is actually due to the mutation in the yvfI gene and not a polar effect of yvfI mutation on the downstream gene. As expected, all resulting lacR mutant derivatives of PY79 still produced bacilysin.


Patient involvement in decision-making: a cross-sectional study in a Malaysian primary care clinic.
Shared decision-making has been advocated as a useful model for patient management. In developing Asian countries such as Malaysia, there is a common belief that patients prefer a passive role in clinical consultation. As such, the objective of this study was to determine Malaysian patients' role preference in decision-making and the associated factors. A cross-sectional study. Study was conducted at an urban primary care clinic in Malaysia in 2012. Patients aged >21 years were chosen using systematic random sampling. Consenting patients answered a self-administered questionnaire, which included demographic data and their preferred and actual role before and after consultation. Doctors were asked to determine patients' role preference. The Control Preference Scale was used to assess patients' role preference. Prevalence of patients' preferred role in decision-making. (1) Actual role played by the patient in decision-making. (2) Sociodemographic factors associated with patients' preferred role in decision-making. (3) Doctors' perception of patients' involvement in decision-making. The response rate was 95.1% (470/494). Shared decision-making was preferred by 51.9% of patients, followed by passive (26.3%) and active (21.8%) roles in decision-making. Higher household income was significantly associated with autonomous role preference (p=0.018). Doctors' perception did not concur with patients' preferred role. Among patients whom doctors perceived to prefer a passive role, 73.5% preferred an autonomous role (p=0.900, κ=0.006). The majority of patients attending the primary care clinic preferred and played an autonomous role in decision-making. Doctors underestimated patients' preference to play an autonomous role.


[Stenting for treatment of scarry stenoses of the esophagus in children].
The article contains results of examination and treatment of 160 children with scarry stenoses of the esophagus. Radical operations were made in 4 children, 4 children were treated by a direct bougieurage, 73 by bougieurage with a thread, in 79 children esophagus stenting was used. Stents of different shape and different methods of their fixation were used. The time of treatment and number of bougieurages in children when stents were used was much less than when only bougieurage was used although the same results were obtained.


Density-dependent dispersal strategies in a cooperative breeder.
Dispersal is a key ecological process that influences the dynamics of spatially and socially structured populations and consists of three stages-emigration, transience, and settlement-and each stage is influenced by different social, individual, and environmental factors. Despite our appreciation of the complexity of the process, we lack a firm empirical understanding of the mechanisms underlying the different stages. Here, using data from 65 GPS-collared dispersing female coalitions of the cooperatively breeding meerkat (Suricata suricatta), we present a comprehensive analysis of the effects of population density, mate availability, dispersing coalition size, and individual factors on each of the three stages of dispersal in a wild population. We expected a positive effect of density on dispersal due to increased kin competition at high densities. We further anticipated positive effects of mate availability, coalition size, and body condition on dispersal success. We observed increasing daily emigration and settlement probabilities at high population densities. In addition, we found that emigration and settlement probabilities also increased at low densities and were lowest at medium densities. Daily emigration and settlement probabilities increased with increasing female coalition size and in the presence of unrelated males. Furthermore, the time individuals spent in the transient stage increased with population density, whereas coalition size and presence of unrelated males decreased dispersal distance. The observed nonlinear relationship between dispersal and population density is likely due to limited benefits of cooperation at low population densities and increased kin competition at high densities. Our study provides empirical validation for the theoretical predictions that population density is an important factor driving the evolution of delayed dispersal and philopatry in cooperative breeders.


Individuals Intolerant of Uncertainty: The Maintenance of Worry and Distress Despite Reduced Uncertainty.
The intolerance of uncertainty model of worry posits that individuals worry as a means to cope with the discomfort they feel when outcomes are uncertain, but few experimental studies have investigated the causal relationships between intolerance of uncertainty, situational uncertainty, and state worry. Furthermore, existing studies have failed to control for the likelihood of future negative events occurring, introducing an important rival hypothesis to explain past findings. In the present study, we examined how individuals with high and low trait intolerance of uncertainty differ in their behavioral, cognitive, and emotional reactions to situational uncertainty about an upcoming negative event (watching emotionally upsetting film clips), holding constant the likelihood of that negative event taking place. We found that although individuals high in trait prospective intolerance of uncertainty reported a higher degree of belief that being provided with detailed information about the upcoming stressor would make them feel more at ease, they did not experience an actual decrease in distress or state worry upon being provided with more information, during anticipation of the film clips, or during the film clips themselves. Our results suggest that heightened distress regarding negative events may be more central than intolerance of uncertainty to the maintenance of worry.


Monumental architecture at Aguada Fénix and the rise of Maya civilization.
Archaeologists have traditionally thought that the development of Maya civilization was gradual, assuming that small villages began to emerge during the Middle Preclassic period (1000-350 BC; dates are calibrated throughout) along with the use of ceramics and the adoption of sedentism1. Recent finds of early ceremonial complexes are beginning to challenge this model. Here we describe an airborne lidar survey and excavations of the previously unknown site of Aguada Fénix (Tabasco, Mexico) with an artificial plateau, which measures 1,400 m in length and 10 to 15 m in height and has 9 causeways radiating out from it. We dated this construction to between 1000 and 800 BC using a Bayesian analysis of radiocarbon dates. To our knowledge, this is the oldest monumental construction ever found in the Maya area and the largest in the entire pre-Hispanic history of the region. Although the site exhibits some similarities to the earlier Olmec centre of San Lorenzo, the community of Aguada Fénix probably did not have marked social inequality comparable to that of San Lorenzo. Aguada Fénix and other ceremonial complexes of the same period suggest the importance of communal work in the initial development of Maya civilization.


Effect of Flavonoids on Oxidative Stress and Inflammation in Adults at Risk of Cardiovascular Disease: A Systematic Review.
Oxidative stress (OS) and inflammatory processes initiate the first stage of cardiovascular disease (CVD). Flavonoid consumption has been related to significantly improved flow-mediated dilation and blood pressure. Antioxidant and anti-inflammatory mechanisms are thought to be involved. The effect of flavonoids on markers of oxidative stress and inflammation, in at risk individuals is yet to be reviewed. Systematic literature searches were conducted in MEDLINE, Cochrane Library, CINAHL and SCOPUS databases. Randomised controlled trials in a Western country providing a food-based flavonoid intervention to participants with one or two modifiable risk factors for CVD measuring a marker of OS and/or inflammation, were included. Reference lists were hand-searched. The Cochrane Collaboration Risk of Bias Tool was used to assess study quality. The search strategy retrieved 1248 articles. Nineteen articles meeting the inclusion criteria were reviewed. Eight studies were considered at low risk of bias. Cocoa flavonoids provided to Type 2 diabetics and olive oil flavonoids to mildly-hypertensive women reduced OS and inflammation. Other food sources had weaker effects. No consistent effect on OS and inflammation across patients with varied CVD risk factors was observed. Study heterogeneity posed a challenge for inter-study comparisons. Rigorously designed studies will assist in determining the effectiveness of flavonoid interventions for reducing OS and inflammation in patients at risk of CVD.


Hepatitis B viral core proteins with an N-terminal extension can assemble into core-like particles but cannot be enveloped.
The structure of hepatitis B virus (HBV) nucleocapsids has been revealed in great detail by cryoelectron microscopy. How nucleocapsids interact with surface antigens to form enveloped virions remains unknown. In this study, core mutants with N-terminal additions were created to address two questions: (1) can these mutant core proteins still form nucleocapsids and (2) if so, can the mutant nucleocapsids interact with surface antigens to form virion-like particles. One plasmid encoding an extra stretch of 23 aa, including six histidine residues, fused to the N terminus of the core protein (designated HisC183) was expressed in Escherichia coli and detected by Western blot. CsCl gradient and electron microscopy analyses indicated that HisC183 could self-assemble into nucleocapsids. When HisC183 or another similar N-terminal fusion core protein (designated FlagC183) was co-expressed with a core-negative plasmid in human hepatoma cells, both mutant core proteins self-assembled into nucleocapsids. These particles also retained kinase activity. Using an endogenous polymerase assay, a fill-in HBV DNA labelled with isotope was obtained from intracellular nucleocapsids formed by mutant cores. In contrast, no such signal was detected from the transfection medium, which was consistent with PCR and Southern blot analyses. Results indicate that core mutants with N-terminal extensions can form nucleocapsids, but are blocked during the envelopment process and cannot form secreted virions. The mutant nucleocapsids generated from this work should facilitate further study on how nucleocapsids interact with surface antigens.


Situation analysis of HIV/AIDS epidemic in sub-Saharan Africa.
At the end of 1997 about twenty one million persons were living with HIV/AIDS in sub-Saharan Africa, representing almost two third of the world's total. Three broadly defined areas, which include countries with severe epidemics and others with epidemics at their intermediate stage, account for almost 90% of all current HIV infections in tropical Africa. According to World Health Organization (WHO), the current data show very high increases in HIV/AIDS incidence as well as serious underreporting of the disease in the last five years. Sub-Saharan Africa has been particularly hard hit by the disease because of a combination of poor social and health education and also because of other endemic sexually transmitted diseases which significantly increase the chance of HIV transmission.


[Parasitic diseases in domestic dogs and cats in the megalopolis of Moscow].
In Moscow, 7 species of helminths and 5 species of protozoa were found in domestic dogs and 6 species of helminths and 6 species of protozoa were detected in domestic cats. Such a great variety in pararistic diseases is distinguished for a low, but steady-state extensity of invasion. The change in socioeconomic relations accompanied by a gradual rise in the number of domestic and stray dogs in the megalopolis may create prerequisites for not only the spread, but also occurrence of parasitic diseases that have not been earlier notified in the city.


Reduction-Oxidation Cascade Strategy for Reforming a Au13-Kerneled Gold Thiolate Nanocluster.
Gold nanoclusters protected by thiolate ligands are ideal models for investigating the structure-property correlation of nanomaterals. Introducing relatively weak coordinating ligands into gold thiolate nanoclusters and thus reforming their structures is beneficial for further releasing their activities. However, controlling the selectivity of the process is a challenging task. In this work, we report a cascade strategy for deeply and purposefully reforming the structures of gold thiolate nanoclusters, exemplified by a Au13-kerneled Au23 nanocluster. Specifically, weakly coordinated triphenylphosphine was utilized to reduce (activate) the surface of Au23, enabling its further structural reformation by the following oxidation step. A structurally distinctive Au20 nanocluster was obtained based on this reduction-oxidation cascade strategy. Mechanism studies reveal that both the reduction and oxidation steps and their working sequence are critical for the transformation. Theoretical and experimental results all indicate that the deep structural reformation results in the evolution of the electronic and photoluminescent properties of the gold thiolate nanocluster.


Atrial Fibrillation Should Guide Prophylactic Tricuspid Procedures During Left Ventricular Assist Device Implantation.
Atrial fibrillation (AF) and tricuspid regurgitation (TR) are common in patients undergoing left ventricular assist device (LVAD) implantation. TR progression is associated with the presence of AF, and questions remain as to who benefits from tricuspid valve procedures (TVPs). We examined the impact of preoperative AF on TR progression after LVAD implantation. From February 2007 to May 2014, 250 patients underwent LVAD implantation at our institution. Patients with concomitant TVP were excluded from this analysis (113 patients). The indication for LVAD was destination therapy in 80 patients (58%) and the etiology of heart failure was ischemic in 73 (53%). Follow-up was available in all early survivors for a total of 393 patient-years of support. Of the 137 non-TVP patients, 52 (38%) had AF preoperatively. Observed overall survival at 1, 3, and 5 years was 82%, 67%, and 55%, respectively. Median grade of TR increased from 2 preoperatively to 3 (p = 0.04) in the AF group and 2.2 (p = 0.75) in the non-AF group at 5 years of follow-up. We also observed a significant difference in the degree of TR between groups at 3 months (p = 0.03) and 12 months (p = 0.01) postimplantation, and a trend toward significance at 18 (p = 0.06) and 24 (p = 0.07) months. The presence of AF is associated with early progression of TR after LVAD implantation. Addition of concomitant TVP in patients with preoperative AF may be considered in patients with less than severe TR. The impact of these findings on right ventricular failure/remodeling remains to be evaluated.


In vitro evaluation of the anti-pathogenic activity of Okoubaka aubrevillei on the human gastrointestinal tract.
Okoubaka aubrevillei is used in traditional West African medicine and in homeopathy for treatment and prevention of several gastrointestinal problems. The aim of this in vitro study was to evaluate the effect of repeated doses of two Okoubaka products (10 % ethanolic tincture, mother tincture (MT); 3rd decimal potency, 3X) on the microbial activity of physiological human colon microbiota using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) and to investigate any preventive effect against infections with diarrhea-causing pathogens. Upon inoculation with fecal microbiota from a healthy donor, 4 parallel proximal colon compartments of the SHIME were treated either with Okoubaka MT, Okoubaka 3X, ethanol control or blank control for 7 days. Using the Okoubaka-adapted microbial community from SHIME, 48 h challenge tests were performed with enterotoxigenic Escherichia coli (ETEC) and Salmonella enteritidis in 4 different doses (103-108 colony forming units as typical in vivo infectious doses). Pathogen concentrations, short-chain fatty acids (SCFAs) and branched SCFA production were measured in triplicate at 0, 24 and 48 h. In the challenge tests, both Okoubaka products were able to restrict the colonization of ETEC and Salmonella at 3 of the 4 pathogen doses (except the highest doses), with a stronger anti-pathogenic effect for MT, which included a reduction of 2.0 log-units of ETEC (p < 0.0001) and 1.1 log-units of Salmonella (p < 0.0001). Total SCFA levels remained unaffected, but butyrate increased during the first 24 h (p < 0.0001 for ETEC), accompanied by decreased acetate production. We observed in vitro a systemic activating effect of Okoubaka on intestinal microbiome resistance, which resulted in an anti-pathogenic effect, especially against ETEC. We hypothesize that the mode of action in vivo is also based on systemic regulative effects.


[Changes in plasma interleukin-33 concentration in sepsis and its correlation with seriousness of sepsis].
To observe the changes in plasma interleukin-33 (IL-33) in patients with sepsis and its regularity, the association between IL-33 and the infection, and the significance of IL-33 in predicting the prognosis of sepsis. A prospective single-center single-blind clinical study was conducted. Forty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medical University from May 2012 to January 2013 were enrolled. The patients were divided into general sepsis, severe sepsis and septic shock groups according to the severity of systemic infection and presence of organ dysfunction. The sepsis patients were again divided into 28-day death group and survival group. Ten healthy volunteers and 11 patients with systemic inflammatory response syndrome (SIRS) were enrolled as healthy control and SIRS groups. The levels of procalcitonin (PCT), IL-33, IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and IL-33 receptor sST2 were determined with enzyme linked immunosorbent assay (ELISA) within 3 hours, and 24 hours and 5 days after enrollment to ICU. The acute physiology and chronic health evaluation II (APACHE II) score was calculated. The clinical outcome, length of stay in ICU, and duration of mechanical ventilation were recorded. The relationship between IL-33 and each parameter was analyzed by Spearman analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate IL-33 in predicting the outcome of sepsis. Plasma IL-33 in sepsis patients within 3 hours after admission was significantly increased compared with that of the healthy controls and SIRS group (ng/L: 15.43±7.22 vs. 0.67±0.24, 1.25±1.09, both P < 0.01). Compared with SIRS group, PCT in sepsis group was significantly increased [μg/L: 52.23 (19.69, 73.37) vs. 1.22 (0.69, 3.73), Z = -2.447, P < 0.001]. With exacerbation of illness, APACHE II score, the values of PCT and IL-33 were gradually increased in general sepsis, severe sepsis and septic shock groups, while the length of stay in ICU and the duration of mechanical ventilation were gradually prolonged (P < 0.05 or P < 0.01). The concentration of IL-33 (ng/L) of sepsis patients admitted to ICU within 3 hours, and 24 hours and 5 days of the illness was 15.43±7.22, 11.82±6.16, 5.55±2.25, respectively (F = 4.823, P = 0.004). There was a positive correction between IL-33 within 3 hours after ICU admission and APACHE II score (r = 0.351, P = 0.031), PCT (r = 0.412, P = 0.005), IL-6 (r = 0.535, P = 0.030), IL-1β (r = 0.674, P = 0.030), TNF-α (r = 0.250, P = 0.030), sST2 (r = 0.620, P < 0.001), and length of stay in ICU (r = 0.296, P = 0.013), duration of mechanical ventilation (r = 0.385, P = 0.011). Decreased plasma IL-33 level could be found in the survivors (n = 37, F = 7.798, P < 0.01), and its level in non-survivors (n = 3) was increased (F = 37.283, P > 0.05). The area under the ROC curve (AUC) of IL-33 and PCT in ROC curve were 0.821, 0.829. When the cut-off value of IL-33 was 13.79 ng/L, the sensitivity was 74.2%, the specificity was 79.6%; when the cut-off value of PCT was 4.70 μg/L, the sensitivity was 87.5%, and the specificity was 81.4%. The concentration of IL-33 3 hours after ICU admission was obviously increased in sepsis patients, and it was positively correlated with PCT, therefore it is valuable in the diagnosis of the infection. In addition plasma IL-33 is related to the severity of sepsis. Its trend of change is valuable in predicting the outcome and in distinguishing sepsis from SIRS.


Isolated fractures of the greater tuberosity in proximal humerus: does the direction of displacement influence functional outcome? An analysis of displacement in greater tuberosity fractures.
The treatment of isolated fractures of the greater tuberosity of the proximal humerus is still debated, especially in the case of minimally dispaced fractures. Differently from other proximal humerus fractures this kind of injury frequently affects young patients with high functional request. The aim of this study is to assess the outcome of patients treated conservatively for greater tubero-sity isolated fractures, comparing the clinical results in patients with different direction of fracture displacement. 38 patients with isolated fracture of greater tuberosity participated to the study and were evaluated at 17 months (10-26) of follow up using Constant Murley Score and DASH Score. Patients were divided in groups with different direction of displacement (10 no displacement, 13 postero-superior, 6 antero-superior and 9 antero-inferior displacement). Patients with no displaced fractures had a mean Constant Murley Score of 82 and a mean DASH Score of 15; those with postero-superior displacement had a mean a Constant Murley Score of 61 and a mean DASH Score of 43; for antero-superior displacement the mean Constant Murley Score was 76 and the mean DASH Score of 18; for the antero-inferiorly displaced the mean Constant Murley Score was 83 and the DASH Score 16. Data suggest that postero-superior displacement leads to poorer outcomes than undisplaced or displaced in other directions fractures treated conservatively.


Community-Acquired Pneumonia in Children.
Community-acquired pneumonia is an important cause of morbidity in developed countries and an important cause of morbidity and mortality in developing countries. Prompt diagnosis and appropriate treatment are very important. To provide an update on the evaluation, diagnosis, and treatment of community-acquired pneumonia in children. A PubMed search was completed in Clinical Queries using the key term "communityacquired pneumonia". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key term "community-acquired pneumonia" from www.google.com/patents, http://espacenet.com, and www. freepatentsonline.com. Generally, viruses, notably respiratory syncytial virus, are the most common cause of community- acquired pneumonia in children younger than 5 years. Streptococcus pneumoniae is the most common bacterial cause across all age groups. Other important bacterial causes in children younger than 5 years include Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus, and Moraxella catarrhalis. In children 5 years or older, in addition to S. pneumoniae, other important bacterial causes include Mycoplasma pneumoniae and Chlamydophila pneumonia. In the majority of cases, bacterial and viral pneumonia cannot be reliably distinguished from each other on clinical grounds. In practice, most children with pneumonia are treated empirically with antibiotics; the choice of which depends on the patient's age and most likely pathogen. Recent patents related to the management of community-acquired pneumonia are discussed. In previously healthy children under the age of 5 years, high dose amoxicillin is the treatment of choice. For those with type 1 hypersensitivity to penicillin, clindamycin, azithromycin, clarithromycin, and levofloxacin are reasonable alternatives. For children with a non-type 1 hypersensitivity to penicillin, cephalosporins such as cefixime, cefprozil, cefdinir, cefpodoxime, and cefuroxime should be considered. In previously healthy children over the age of 5 years, macrolides such as azithromycin and clarithromycin are the drugs of choice.


Anniversary Narratives of the Health Care State: Institutional Entrenchment in Retrospect.
Institutional narratives, appealing both to the intellect and the imagination, are powerful mechanisms of entrenchment. Drawing on close examination of legislative debates, interview transcripts, and official documents, this article analyzes institutional narratives of the British National Health Service (NHS) and American Medicare and Medicaid. These narratives take the form of epics, featuring founding heroes, adversaries, stewards, saviors, and other characters, and are retold on multiple occasions, and especially on anniversaries of the founding date. In the process, certain elements of history are remembered, and others forgotten. The myth of the NHS as a single national institution obscured much of the complexity and compromise that went into its founding and subsequent development, but preserved fidelity to its founding principles. In the United States, the dominant narrative belonged to Medicare, while Medicaid featured as an afterthought. In the case of the NHS, narrative entrenchment served to preserve universal access to comprehensive health care. In the case of American Medicare, entrenchment preserved the original mission of the institution but kept it from expanding to a broader swath of the population, even as its less-entrenched companion Medicaid provided a vehicle for coverage of an increasingly wide range of population groups. A distinct Medicaid narrative developed only after incremental expansion was well underway.


Actomyosin-generated tension controls the molecular kinetics of focal adhesions.
Focal adhesions (FAs) have key roles in the interaction of cells with the extracellular matrix (ECM) and in adhesion-mediated signaling. These dynamic, multi-protein structures sense the ECM both chemically and physically, and respond to external and internal forces by changing their size and signaling activity. However, this mechanosensitivity is still poorly understood at the molecular level. Here, we present direct evidence that actomyosin contractility regulates the molecular kinetics of FAs. We show that the molecular turnover of proteins within FAs is primarily regulated by their dissociation rate constant (k(off)), which is sensitive to changes in forces applied to the FA. We measured the early changes in k(off) values for three FA proteins (vinculin, paxillin and zyxin) upon inhibition of actomyosin-generated forces using two methods - high temporal resolution FRAP and direct measurement of FA protein dissociation in permeabilized cells. When myosin II contractility was inhibited, the k(off) values for all three proteins changed rapidly, in a highly protein-specific manner: dissociation of vinculin from FAs was facilitated, whereas dissociation of paxillin and zyxin was attenuated. We hypothesize that these early kinetic changes initiate FA disassembly by affecting the molecular turnover of FAs and altering their composition.


Cytokine responses to various larval stages of equine strongyles and modulatory effects of the adjuvant G3 in vitro.
To generate different larval stages of Strongylus vulgaris and to study cytokine responses in cultures of eqPBMC exposed to defined larval stages of S. vulgaris and cyathostomins with the aim to understand the early immune reaction to these parasites. EqPBMC were exposed to S. vulgaris larvae (L3, exsheated L3 and L4) and cyathostomin L3 and analysed for cytokine gene expression. Procedures for decontamination, culturing and attenuation of larvae were established. Transcription of IL-4, IL-5 and IL-13 was induced by both S. vulgaris and cyathostomin L3. Moulting of S. vulgaris from L3 to L4 stage was accompanied by a shift to high expression of IL-5 and IL-9 (exsheated L3 and L4) and IFN-γ (L4 only). In parallel, the adjuvant G3 modified the cytokine profile induced by both parasites by reducing the expression of IL-4, IL-5 and IL-10 while concomitantly enhancing the expression of IFN-γ. The L4 stage of S. vulgaris generated a cytokine profile different from that induced by the earlier L3 stage of S. vulgaris and cyathostomins. This diversity depending on the life cycle stage will have implications for the choice of antigen and adjuvant in future vaccine design.


[Frailty in older population: a brief position paper from the French society of geriatrics and gerontology].
Frailty in the older population is a clinical syndrome which evaluate a risk level. The Frailty syndrome defines a reduction of the adaptation capacity to a stress. It can be modulated by physical, psychological and social factors. The screening of the frailty syndrome is relevant for older people without disability for basic activities of daily living. The clinical criteria of frailty must be predictive of the risk of functional decline and adverse outcomes, consensual at the international level, and easy to perform in primary care as well as in the clinical researches.


RNA interference in Nilaparvata lugens (Homoptera: Delphacidae) based on dsRNA ingestion.
An efficient and convenient RNA interference (RNAi) technique involving double-stranded RNA (dsRNA) ingestion is useful for gene function studies of non-model insects. Three dsRNAs targeting different sites within a gene encoding vacuolar ATP synthase subunit E (V-ATPase-E, 21E01) were synthesised for RNAi in Nilaparvata lugens. dsRNA was found to be stable in 0.1 g mL(-1) sucrose solution, but unstable in artificial fodder. Therefore, dsRNAs were orally delivered into N. lugens in 0.1 g mL(-1) sucrose solution. RNAi was induced by all three of the dsRNAs at 0.05 µg µL(-1) in N. lugens. Time dynamics analysis of gene silencing indicated that significant suppression of the target gene began as early as 2 days after ingestion of ds2-21E01 and ds3-21E01. However, significant repressive effects were recorded up to 10 days after exposure to ds1-21E01. The maximum reduction in target gene mRNA was observed after 10 days of treatment, with suppression ratios induced by ds1-21E01, ds2-21E01 and ds3-21E01 of 41, 55 and 48% respectively. An efficient and convenient RNAi technique involving dsRNA ingestion has been successfully developed for N. lugens. This will be a useful tool for further functional genomic investigation in this organism.


Opportunistic pulmonary strongyloidiasis complicating asthma treated with steroids.
A man aged 57 years who had lived most of his life in London, suffered from asthma which had begun during army service in Burma 37 years previously. Latterly he was treated with increasing doses of corticosteroids but his symptoms continued to worsen and he died of asthma. Necropsy revealed a heavy opportunistic infection of the bronchi and lungs by the nematode Strongyloides stercoralis which he had presumably acquired while on service abroad. The case illustrates the need, even in non-endemic areas, to suspect opportunistic pulmonary strongyloidiasis when a patient's asthma worsens despite treatment with increasing doses of corticosteroids. Although it is a potentially lethal iatrogenic opportunistic infection, it is amenable to treatment with anthelminthic agents if recognized in time.


[Therapy of common cold with a homeopathic combination preparation in comparison with acetylsalicylic acid. A controlled, randomized double-blind study].
A clinical test was carried out on 170 West German army soldiers suffering from common cold. The test was conducted on a monocentric, randomized, non-sequential, and inter-individual basis; the research workers were kept blind on the identity of the medication. The purpose of testing was to compare the effectiveness of a combination homeopathic preparation (Gripp-Heel) with that of acetylsalicylic acid. On the 4th and 10th treatment days, no significant difference was determined with respect to changes in clinical findings, subjectively assessed complaints, or length of time the patients were unable to work. Thus the two preparations possess comparative effectiveness in the treatment of the common cold.


A strategy for enhancing bioactivity and osseointegration with antibacterial effect by incorporating magnesium in polylactic acid based biodegradable orthopedic implant.
Biodegradable orthopedic implants are essential for restoring the physiological structure and function of bone tissue while ensuring complete degradation after recovery. Polylactic acid (PLA), a biodegradable polymer, is considered a promising material due to its considerable mechanical properties and biocompatibility. However, further improvements are necessary to enhance the mechanical strength and bioactivity of PLA for reliable load-bearing orthopedic applications. In this study, a multifunctional PLA-based composite was fabricated by incorporating tricalcium phosphate (TCP) microspheres and magnesium (Mg) particles homogenously at a volume fraction of 40 %. This approach aims to enhance mechanical strength, accelerate pore generation, and improve biological and antibacterial performance. Mg content was incorporated into the composite at varying values of 1, 3, and 5 vol% (referred to as PLA/TCP-1 Mg, PLA/TCP-3 Mg, and PLA/TCP-5 Mg, respectively). The compressive strength and stiffness were significantly enhanced in all composites, reaching 87.7, 85.9, and 84.1 MPa, and 2.7, 3.0, and 3.1 GPa, respectively. The degradation test indicated faster elimination of the reinforcers as the Mg content increased, resulting in accelerated pore generation to induce enhanced osseointegration. Because PLA/TCP-3 Mg and PLA/TCP-5 Mg exhibited cracks in the PLA matrix due to rapid corrosion of Mg forming corrosion byproducts, to optimize the Mg particle content, PLA/TCP-1 Mg was selected for further evaluation. As determined by in vitro biological and antibacterial testing, PLA/TCP-1 Mg showed enhanced bioactivity with pre-osteoblast cells and exhibited antibacterial properties by suppressing bacterial colonization. Overall, the multifunctional PLA/TCP-Mg composite showed improved mechanobiological performance, making it a promising material for biodegradable orthopedic implants.


Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: longitudinal assessment during the first 15 months of corrected age.
Very low birth weight (VLBW) infants (< 1,500 g) with bronchopulmonary dysplasia (BPD) develop lung damage caused by mechanical ventilation and maturational arrest. We compared functional lung development after discharge from hospital between VLBW infants with and without BPD. Comprehensive lung function assessment was performed at about 50, 70, and 100 weeks of postmenstrual age in 55 sedated VLBW infants (29 with former BPD [O2 supplementation was given at 36 weeks of gestational age] and 26 VLBW infants without BPD [controls]). Mean gestational age (26 vs. 29 weeks), birth weight (815 g vs. 1,125 g), and the proportion of infants requiring mechanical ventilation for ≥7 d (55% vs. 8%), differed significantly between BPD infants and controls. Both body weight and length, determined over time, were persistently lower in former BPD infants compared to controls, but no significant between-group differences were noted in respiratory rate, respiratory or airway resistance, functional residual capacity as determined by body plethysmography (FRC(pleth)), maximal expiratory flow at the FRC (V'max (FRC)), or blood gas (pO2, pCO2) levels. Tidal volume, minute ventilation, respiratory compliance, and FRC determined by SF6 multiple breath washout (representing the lung volume in actual communication with the airways) were significantly lower in former BPD infants compared to controls. However, these differences became non-significant after normalization to body weight. Although somatic growth and the development of some lung functional parameters lag in former BPD infants, the lung function of such infants appears to develop in line with that of non-BPD infants when a body weight correction is applied. Longitudinal lung function testing of preterm infants after discharge from hospital may help to identify former BPD infants at risk of incomplete recovery of respiratory function; such infants are at risk of later respiratory problems.


Bioactive Plant Metabolites in the Management of Non-Communicable Metabolic Diseases: Looking at Opportunities beyond the Horizon.
There has been an unprecedented worldwide rise in non-communicable metabolic diseases (NCDs), particularly cardiovascular diseases (CVD) and diabetes. While modern pharmacotherapy has decreased the mortality in the existing population, it has failed to stem the rise. Furthermore, a large segment of the world population cannot afford expensive pharmacotherapy. Therefore, there is an urgent need for inexpensive preventive measures to control the rise in CVD and diabetes and associated co-morbidities. The purpose of this review is to explore the role of food bioactives in prevention of NCDs. To this end, we have critically analyzed the possible utility of three classes of food bioactives: (a) resistant starch, a metabolically resistant carbohydrate known to favorably modulate insulin secretion and glucose metabolism; (b) cyclo (His-Pro), a food-derived cyclic dipeptides; and (c) polyphenol-rich berries. Finally, we have also briefly outlined the strategies needed to prepare these food-bioactives for human use.


Building policy capacities: an interactive approach for linking knowledge to action in health promotion.
This article outlines a theoretical framework for an interactive, research-driven approach to building policy capacities in health promotion. First, it illustrates how two important issues in the recent public health debate, capacity building and linking scientific knowledge to policy action, are connected to each other theoretically. It then introduces an international study on an interactive approach to capacity building in health promotion policy. The approach combines the ADEPT model of policy capacities with a co-operative planning process to foster the exchange of knowledge between policy-makers and researchers, thus improving intra- and inter-organizational capacities. A regional-level physical activity promotion project involving governmental and public-law institutions, NGOs and university researchers serves as a case study to illustrate the potential of the approach for capacity building. Analysis and comparison with a similar local-level project indicate that the approach provides an effective means of linking scientific knowledge to policy action and to planning concrete measures for capacity building in health promotion, but that it requires sufficiently long timelines and adequate resources to achieve adequate implementation and sustainability.


Anisotropic scaffolds facilitate enhanced neurite extension in vitro.
Tissue engineering (TE) techniques to enhance nerve regeneration following nerve damage have had limited success in matching the performance of autografts across short nerve gaps (< 10 mm). For regeneration over longer nerve gaps, TE techniques have been less successful than autografts. Most engineered scaffolds do not present directional cues to the regenerating nerves. In our efforts to design a TE scaffold to replace the autograft, we hypothesize that anisotropic hydrogel scaffolds with gradients of a growth-promoting glycoprotein, laminin-1 (LN-1), may promote directional neurite extension and enhance regeneration. In this study we report the engineering of three-dimensional (3D) agarose scaffolds with photoimmobilized gradients of LN-1 of differing slopes. Dorsal root ganglia (DRG) from chicken embryos were cultured in the agarose scaffolds and their neurite extension rate was determined. DRG neurite extension rates were significantly higher in the anisotropic scaffolds, with a maximal growth rate in an anisotropic scaffold twice that of the maximal growth rate in isotropic scaffolds of LN-1. We suggest that these anisotropic scaffolds, presenting an optimal gradient of LN-1, may significantly impact nerve regeneration. Such anisotropic scaffolds may represent a new generation of tissue engineered materials with built-in directional cues for guided tissue or nerve regeneration.


Pericardiocentesis Outcomes in Patients With Pulmonary Hypertension: A Nationwide Analysis from the United States.
Pericardiocentesis (PC) in patients with pulmonary hypertension (PH) and pericardial effusions has unclear benefits because it has been associated with acute hemodynamic collapse and increased mortality. Data on in-hospital outcomes in this population are limited. The National Inpatient Sample database was used to identify adult patients who underwent PC during hospitalizations between 2016 and 2020. Data were stratified by the presence or absence of PH. A multivariate regression model and case-control matching was used to estimate the association of PH with PC in-hospital outcomes. A total of 95,665 adults with a procedure diagnosis of PC were included, of whom 7,770 had PH. Patients with PH tended to be older (aged 67 ± 15.7 years) and female (56%) and less frequently presented with tamponade (44.9% vs 52.4%). Patients with PH had significantly higher rates of chronic kidney disease, coronary artery disease, heart failure, and chronic lung disease, among other co-morbidities. In the multivariate analysis, PC in PH was associated with higher all-cause mortality (adjusted odds ratio [aOR] 1.40, confidence interval [CI] 1.30 to 1.51) and higher rates of postprocedure shock (aOR 1.53, CI 1.30 to 1.81) than patients without PH. Mortality was higher in those with pulmonary arterial hypertension than other nonpulmonary arterial hypertension PH groups (aOR 2.35, 95% CI 1.46 to 3.80, p <0.001). The rates of cardiogenic shock (aOR 1.49, 95% CI 1.38 to 1.61), acute respiratory failure (aOR 1.56, 95% CI 1.48 to 1.64), and mechanical circulatory support use (aOR 1.86, 95% CI 1.63 to 2.12) were also higher in patients with PH. There was no significant volume-outcome relation between hospitals with a high per-annum pericardiocentesis volume compared with low-volume hospitals in these patients. In conclusion, PC is associated with increased in-hospital mortality and higher rates of cardiovascular complications in patients with PH, regardless of the World Health Organization PH group.


Recognizing victims of human trafficking in the pediatric emergency department.
Human trafficking is a form of modern-day slavery that is rapidly expanding in the United States and throughout the world. It is a crime under both the United States and international law. The child and adult victims of human trafficking are denied their basic human rights and subjected to unspeakable physical and emotional harm. Traffickers exert complete control over their victims and are proficient at hiding their condition from authorities. Healthcare practitioners may be the only professionals who come into contact with victims if they present for medical care. This article will describe human trafficking and its potential victims, as well as guide medical management and access to services that will ensure their safety and restore their freedom.


Characterization of Microbial Communities in Pilot-Scale Constructed Wetlands with Salicornia for Treatment of Marine Aquaculture Effluents.
Microorganisms play an essential role in the performance of constructed wetlands (CWs) for wastewater treatment. However, there has been limited discussion on the characteristics of microbial communities in CWs for treatment of effluents from marine recirculating aquaculture systems (RAS). This study is aimed at characterizing the microbial communities of pilot-scale CWs with Salicornia bigelovii for treatment of saline wastewater from a land-based Atlantic salmon RAS plant located in Northern China. Illumina high-throughput sequencing was employed to identify the profile of microbial communities of three CWs receiving wastewater under different total ammonia nitrogen (TAN) concentrations. Results of this study showed remarkable spatial variations in diversity and composition of microbial communities between roots and substrates in three CWs, with distinct response to different TAN concentrations. In particular, Proteobacteria, Firmicutes, Cyanobacteria, and Bacteroidetes were predominant in roots, while Cyanobacteria, Proteobacteria, Firmicutes, Verrucomicrobia, and Bacteroidetes were prevalent in substrates. Moreover, redundancy analysis indicated that specific functional genera, such as Nitrosopumilus, Vibrio, Pseudoalteromonas, Nitrospina, and Planctomyces, played key roles in the removal of nitrogen/phosphorus pollutants and growth of wetland plants. From a microorganism perspective, the findings of this study could contribute to better understanding of contaminants' removal mechanism and improved management of CWs for treatment of effluents from land-based marine aquaculture.


Consensus conference definitions and recommendations on intra-abdominal hypertension (iah) and the abdominal compartment syndrome (acs) - the long road to the final publications, how did we get there?
There has been an exponentially increasing interest in intraabdominal hypertension (IAH) and the abdominal compartment syndrome (ACS) over the last decade, and different definitions have been suggested. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. An international multidisciplinary group of interested doctors met with the goal of agreeing on a set of definitions that could be applied to patients with IAH and ACS. The goal of this consensus group was to provide a conceptual and practical framework to further define ACS, a progressive injurious process that falls under the generalized term 'IAH' and that includes IAH-associated organ dysfunction. In total, 21 North American, Australasian and European surgical, trauma and critical care specialists agreed to standardize the current definitions for IAH, ACS and related conditions in preparation for the second World Congress on Abdominal Compartment Syndrome (WCACS). The WCACS-meeting was endorsed by the European Society of Intensive Care Medicine (ESICM) and the World Society on Abdominal Compartment Syndrome (WSACS). The consensus conference (Noosa, Australia; December 7, 2004) was attended by 21 specialists from Europe, Australasia and North America and approximately 70 other congress participants. In advance of the conference, a blueprint for the various definitions was suggested. After the conference the participants corresponded electronically with feedback. A writing committee was formed at the conference and developed the final manuscript based on executive summary documents generated by each participant. The final report of the 2004 International ACS Consensus Definitions Conference has recently been published. This article will describe the long road towards this final publication with the evolution of the different definitions and recommendations from the initial suggestions in 2004 to the further refinement and final publications in 2006 and 2007. It will try to explain how we got there and will also give the percentage of agreement with each proposed definition by the participants. New definitions were offered for some terms, while others were discarded and not kept in the final manuscript. Different cut-offs for defining IAH and ACS were given, as well as broad definitions of primary, secondary and recurrent IAH/ACS. A classification system was introduced taking into account the duration, origin, and etiology of IAH. The use of an organ severity scoring method, by means of the Sequential Organ Failure Assessment (SOFA) score when dealing with ACS patients was not recommended as an adjunctive tool to assess morbidity in the final publication. This document reflects a process whereby a group of experts and opinion leaders suggested definitions for IAH and ACS. This document should be used as a reference for the next consensus definitions conference in March 2007.


Salinimicrobium nanhaiense sp. nov. and Salinimicrobium oceani sp. nov., two novel species of the family Flavobacteriaceae isolated from the South China Sea.
Strains J15B81-2T and J15B91T were isolated from a sediment sample collected from the South China Sea. Cells of both strains were observed to be rod-shaped, non-gliding, Gram-stain-negative, yellow-pigmented, facultatively anaerobic, catalase-positive, oxidase-negative and showing optimum growth at 30 °C. Strains J15B81-2T and J15B91T could tolerate up to 9 and 10 % (w/v) NaCl concentration and grow at pH 6.5-9.5 and 6.0-9.0, respectively. The strains shared 97.4 % 16S rRNA gene sequence similarity to each other but were identified as two distinct species based on 81.1-85.8 % ANIb and 31.5 % dDDH values calculated using whole genome sequences. Strains J15B81-2T and J15B91T shared highest 16S rRNA gene sequence similarity to Salinimicrobium xinjiangense CGMCC 1.12522T (98.4 %) and Salinimicrobium sediminis CGMCC 1.12641T (98.0 %), respectively. Among species with validly published names, S. sediminis CGMCC 1.12641T shared close genetic relatedness with strains J15B81-2T [85.1-85.3% average nucleotide identity based on blastBlast+ (ANIb) and 30.6 % digital DNA-DNA hybridization (dDDH)] and J15B91T (76.6-79.1 % ANIb and 21.5 % dDDH). The major fatty acid of strains J15B81-2T and J15B91T were identified as iso-C15 : 0 and iso-C16 : 0, respectively, and the major polar lipids of the two strains consisted of phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid and one unidentified lipid. The strains contained MK-6 as their predominant menaquinone. The genomic G+C contents of strains J15B81-2T and J15B91T were determined to be 41.7 and 41.8 mol %, respectively. Both strains are considered to represent two novel species of the genus Salinimicrobium and the names Salinimicrobium nanhaiense sp. nov. and Salinimicrobium oceani sp. nov. are proposed for strains J15B81-2T (=KCTC 72867T=MCCC 1H00410T) and J15B91T (=KCTC 72869T=MCCC 1H00411T), respectively.


Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian.
We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain-related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4, 5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been detected in various HLA-homozygous B cell lines. Here we present allele frequencies for this trimeric short tandem repeat (STR) in 604 unrelated individuals collected from nine human populations (Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using the polymerase chain reaction (PCR) combined with fluorescent-based automated fragment detection technology. All alleles were present in each population, but allelic distributions varied from one population to another. No new alleles (such as A7 or A8) were identified. The evolutionary and structural significance of these data as well as the potential application to forensic medicine is discussed.


Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review.
The monoclonal antibody alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in multiple sclerosis (MS) patients when compared to β-interferon. The development of autoimmune diseases, including thyroid disease, has been reported in the literature with a frequency of 20 to 30%. In this article, we describe 4 cases of alemtuzumab-induced thyroid disease in patients with MS. We also performed a systematic review of the available literature. Four patients who had received alemtuzumab for MS and subsequently developed thyroid dysfunction are presented. We compared our patients' clinical courses and outcomes to established disease patterns. We also undertook a systematic review of the published literature. All 4 patients presented with initial hyperthyroidism associated with elevated thyroid-stimulating hormone (TSH) receptor antibodies (TRAb). In 2 cases, hyperthyroidism did not remit after a total of 24 months of carbimazole therapy, and they subsequently underwent subtotal thyroidectomy. The third case subsequently developed biochemical hypothyroidism and required thyroxine replacement, despite having a markedly raised initial TRAb titer. Autoimmunity following alemtuzumab therapy in MS appears to occur as part of an immune reconstitution syndrome and is more likely in smokers who have a family history of autoimmune disease. Management of alemtuzumab-induced thyroid disease is similar to the management of "wild-type" Graves' disease. The use of alemtuzumab in this setting will necessitate close monitoring of thyroid function and early intervention when abnormalities are developing.


Estimating remaining life expectancy in veterans with basal cell carcinoma using an automated electronic health record scoring system: A retrospective cohort study.
Active surveillance may be considered for low-risk basal cell carcinomas (BCCs) in patients with limited life expectancy; however, estimates of life expectancy are not readily available. Veterans Health Administration's Care Assessment Need (CAN) score may address this problem. We examined the CAN score's performance in predicting 1-, 3-, and 5-year mortality in US veterans with BCC. This retrospective cohort study used national Veterans Health Administration's electronic medical record data. The CAN score's performance in the prediction of mortality in veterans with BCC was evaluated based on tests of goodness-of-fit, discrimination, and calibration. For 54,744 veterans with BCC treatment encounters between 2013 and 2018, the CAN score performed well in the prediction of mortality based on multiple tests. A threshold CAN score of 90 had a positive predictive value of 55% for 3-year mortality, clinically useful in identifying patients with intermediate-term survival. The study relied upon the combination of diagnosis codes and procedure codes to identify BCC cases. The CAN score has the potential to improve the quality of cancer care for veterans by providing clinicians with an estimate of life expectancy and facilitating conversations in cases where active surveillance can be considered.


Online interpretable dynamic prediction models for postoperative delirium after cardiac surgery under cardiopulmonary bypass developed based on machine learning algorithms: A retrospective cohort study.
Postoperative delirium (POD) is strongly associated with poor early and long-term prognosis in cardiac surgery patients with cardiopulmonary bypass (CPB). This study aimed to develop dynamic prediction models for POD after cardiac surgery under CPB using machine learning (ML) algorithms. From July 2021 to June 2022, clinical data were collected from patients undergoing cardiac surgery under CPB at Nanjing First Hospital. A dataset from the same center (October 2022 to November 2022) was also used for temporal external validation. We used ML and deep learning to build models in the training set, optimized parameters in the test set, and finally validated the best model in the validation set. The SHapley Additive exPlanations (SHAP) method was introduced to explain the best models. Of the 885 patients enrolled, 221 (25.0%) developed POD. 22 (22.0%) of 100 validation cohort patients developed POD. The preoperative and postoperative artificial neural network (ANN) models exhibited optimal performance. The validation results demonstrated satisfactory predictive performance of the ANN model, with area under the receiver operator characteristic curve (AUROC) values of 0.776 and 0.684 for the preoperative and postoperative models, respectively. Based on the ANN algorithm, we constructed dynamic, highly accurate, and interpretable web risk calculators for POD. We successfully developed online interpretable dynamic ANN models as clinical decision aids to identify patients at high risk of POD before and after cardiac surgery to facilitate early intervention or care.


Methane oxidation over mixed-conducting SrFe(Al)O3-delta-SrAl2O4 composite.
The steady-state CH4 conversion by oxygen permeating through mixed-conducting (SrFe)0.7(SrAl2)0.3Oz composite membranes, comprising strontium-deficient SrFe(Al)O3-delta perovskite and monoclinic SrAl2O4-based phases, occurs via different mechanisms in comparison to the dry methane interaction with the lattice oxygen. The catalytic behavior of powdered (SrFe)0.7(SrAl2)0.3Oz, studied by temperature-programmed reduction in dry CH4 at 523-1073 K, is governed by the level of oxygen nonstoichiometry in the crystal lattice of the perovskite component and is qualitatively similar to that of other perovskite-related ferrites, such as Sr0.7La0.3Fe0.8Al0.2O3-delta. While extensive oxygen release from the ferrite lattice at 700-900 K leads to predominant total oxidation of methane, significant selectivity to synthesis gas formation, with H2/CO ratios close to 2, is observed above 1000 K, when a critical value of oxygen deficiency is achieved. The steady-state oxidation over dense membranes at 1123-1223 K results, however, in prevailing total combustion, particularly due to excessive oxygen chemical potential at the membrane surface. In combination with surface-limited oxygen permeability, mass transport limitations in a porous layer at the membrane permeate side prevent reduction and enable stable operation of (SrFe)0.7(SrAl2)0.3Oz membranes under air/methane gradient. Taking into account the catalytic activity of SrFeO3-delta-based phases for the partial oxidation of methane to synthesis gas and the important role of mass transport-related effects, one promising approach for membrane development is the fabrication of thick layer of porous ferrite-based catalyst at the surface of dense (SrFe)0.7(SrAl2)0.3Oz composite.


Strategies to augment volitional and reflex function may improve locomotor capacity following incomplete spinal cord injury.
Many studies highlight the remarkable plasticity demonstrated by spinal circuits following an incomplete spinal cord injury (SCI). Such plasticity can contribute to improvements in volitional motor recovery, such as walking function, although similar mechanisms underlying this recovery may also contribute to the manifestation of exaggerated responses to afferent input, or spastic behaviors. Rehabilitation interventions directed toward augmenting spinal excitability have shown some initial success in improving locomotor function. However, the potential effects of these strategies on involuntary motor behaviors may be of concern. In this article, we provide a brief review of the mechanisms underlying recovery of volitional function and exaggerated reflexes, and the potential overlap between these changes. We then highlight findings from studies that explore changes in spinal excitability during volitional movement in controlled conditions, as well as altered kinematic and behavioral performance during functional tasks. The initial focus will be directed toward recovery of reflex and volitional behaviors following incomplete SCI, followed by recent work elucidating neurophysiological mechanisms underlying patterns of static and dynamic muscle activation following chronic incomplete SCI during primarily single-joint movements. We will then transition to studies of locomotor function and the role of altered spinal integration following incomplete SCI, including enhanced excitability of specific spinal circuits with physical and pharmacological interventions that can modulate locomotor output. The effects of previous and newly developed strategies will need to focus on changes in both volitional function and involuntary spastic reflexes for the successful translation of effective therapies to the clinical setting.


Project study on Japanese encephalitis vaccination at Gogamukh, Assam.
The aim of the study was to apprise the benefit derived from vaccination against Japanese encephalitis (JE) in Assam. The study was conducted during 1988-1989 with special emphasis on serodiagnosis. Out of total of 22,441 vaccinations, 12,935 belonged to the age group of 5 to 15 years and the rest to 16-25 years. Second and third doses of vaccination were given at 7-14 days and 35-40 days, respectively to 17,336 and 14,605 persons. The protective antibody titre of the blood sample from 5% of the targeted population was assessed. Neutralising antibodies were positive in 245 out of total 261 persons tested before vaccination and was negative in 16. Following vaccination neutralising antibodies were seen in all samples. Even in persons with pre-existing antibodies, a rise in titre was seen after vaccination.


A framework for synthesis of safety justification for digitally enabled healthcare services.
Digitally enabled healthcare services combine socio-technical resources to deliver the required outcomes to patients. Unintended operation of these services may result in adverse effects to the patient. Eliminating avoidable harm requires a systematic way of analysing the causal conditions, identifying opportunities for intervention. Operators of such services may be required to justify, and communicate, their safety. For example, the UK Standardisation Committee for Care Information (SCCI) standards 0129 and 0160 require a safety justification for health IT (superseded versions were known as the Information Standards Board (ISB) 0129 & 0160. Initial as well as current standards are maintained by the NHS Digital. A framework was designed, and applied as proof of concept, to an IT-supported clinical emergencies (A&E) service. Evaluation was done qualitatively based on the authors' experience, identifying potential benefits of the approach. The applied framework encapsulates analysis, and structures the generated information, into a skeleton of an evidence-based case for safety. The framework improved management of the safety activities, assigning ownership to stakeholders (e.g. IT developer), also creating a clear and compelling safety justification. Application of the framework significantly contributed to systematising an exploratory approach for analysing the service, in addition to existing methods such as reporting. Its application made the causal chain to harm more diaphanous. Constructing a safety case contributed to: (a) identifying potential assurance gaps, (b) planning production of information and evidence, and (c) communication of the justification by graphical unambiguous means.


Maternal and neonatal trauma following operative vaginal delivery.
Operative vaginal delivery (OVD) is considered safe if carried out by trained personnel. However, opportunities for training in OVD have declined and, given these shifts in practice, the safety of OVD is unknown. We estimated incidence rates of trauma following OVD in Canada, and quantified variation in trauma rates by instrument, region, level of obstetric care and institutional OVD volume. We conducted a cohort study of all singleton, term deliveries in Canada between April 2013 and March 2019, excluding Quebec. Our main outcome measures were maternal trauma (e.g., obstetric anal sphincter injury, high vaginal lacerations) and neonatal trauma (e.g., subgaleal hemorrhage, brachial plexus injury). We calculated adjusted and stabilized rates of trauma using mixed-effects logistic regression. Of 1 326 191 deliveries, 38 500 (2.9%) were attempted forceps deliveries and 110 987 (8.4%) were attempted vacuum deliveries. The maternal trauma rate following forceps delivery was 25.3% (95% confidence interval [CI] 24.8%-25.7%) and the neonatal trauma rate was 9.6 (95% CI 8.6-10.6) per 1000 live births. Maternal and neonatal trauma rates following vacuum delivery were 13.2% (95% CI 13.0%-13.4%) and 9.6 (95% CI 9.0-10.2) per 1000 live births, respectively. Maternal trauma rates remained higher with forceps than with vacuum after adjustment for confounders (adjusted rate ratio 1.70, 95% CI 1.65-1.75) and varied by region, but not by level of obstetric care. In Canada, rates of trauma following OVD are higher than previously reported, irrespective of region, level of obstetric care and volume of OVD among hospitals. These results support a reassessment of OVD safety in Canada.


No face-down positioning and broad internal limiting membrane peeling in the surgical repair of idiopathic macular holes.
To demonstrate the efficacy of broad internal limiting membrane (ILM) peeling and 20% sulfur hexafluoride (SF6) endotamponade with no face-down positioning in the surgical repair of idiopathic macular holes (MHs). Retrospective study. Sixty-eight idiopathic MH cases in 68 eyes of 65 patients. All idiopathic MH surgeries by 1 surgeon between March 2009 and December 2012, performed using broad ILM peeling, 20% SF6, and no face-down positioning, were reviewed. No cases were excluded. Surgeon method included 23-gauge or 25-gauge pars plana vitrectomy with induction of posterior vitreous detachment (if necessary). Indocyanine green dye (0.08 mg/ml in D5W) was injected slowly, allowed to stain for 60 seconds, and then removed. The ILM was broadly peeled to the vascular arcades (approximately 8000 μm in diameter), followed by 2 fluid-air exchanges, separated by 5 minutes, and an air-20% SF6 exchange. Patients maintained reading position for 3 to 5 days and were followed up at least for 1 month. Exact binomial distributions were used to establish 95% confidence intervals, and the 1-way analysis of variance was used to compare preoperative and postoperative intraocular pressures (IOPs). Single-procedure MH closure rate, mean postoperative best-corrected visual acuity (BCVA), incidence of cataract, and IOP. Three patients (4.6%) had bilateral MH and 9 patients (13.8%) had recurrent MH (mean duration from previous surgery, 8.3 ± 5.5 years; range, 1-16 years). Twenty-one MH (30.9%) were stage 2, 27 (39.7%) were stage 3, and 20 (29.4%) were stage 4. Five MH had a basal diameter of more than 1000 μm. Mean MH basal diameter was 609.6 ± 226.2 μm. Mean preoperative BCVA was 0.68 ± 0.29 logarithm of the minimum angle of resolution (logMAR) units (Snellen equivalent, 20/95), and mean most recent postoperative BCVA was 0.28 ± 0.18 logMAR units (Snellen equivalent, 20/38). The single-procedure MH closure rate was 100% (95% confidence interval, 95%-100%), and no complications were observed. Macular hole surgery with broad ILM peeling, 20% SF6 gas, and no face-down positioning is highly effective in the surgical treatment of idiopathic MH with efficacy comparable with methods that use longer-acting gas endotamponade, face-down positioning, or both. In our series, this method eliminated the morbidity associated with postoperative face-down positioning. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Effects of long-acting thyroid stimulator (LATS) and LATS protector on human thyroid adenyl cyclase activity.
The long-acting thyroid stimulator (LATS) has been thought to be responsible for the hyperthyroidism of Graves's disease. It is detected by its effect on the mouse thyroid gland but cannot be found in all patients with hyperthyroidism. In an attempt to clarify the problem of LATS-negative hyperthyroidism, serum was obtained from untreated patients and its effect in vitro on human thyroid tissue examined, using the activation of adenyl cyclase as a measure of stimulation. Human thyroid adenyl cyclase was activated by both thyroid-stimulating hormone (TSH) and LATS. Thyroid tissue obtained from patients with Graves's disease was relatively less responsive to LATS than was non-toxic thyroid tissue. Of the 24 samples studied five contained LATS and all of these activated adenyl cyclase. The presence of LATS protector in LATS-negative hyperthyroid patients was confirmed but LATS-negative sera had no effect on human thyroid adenyl cyclase activity.


Semiconducting quantum confined silicon-tin alloyed nanocrystals prepared by ns pulsed laser ablation in water.
Here we demonstrate the material's synthetic feasibility for semiconducting alloyed silicon-tin nanocrystals (SiSn-NCs) with quantum confinement effects. An environmentally friendly synthesis is achieved by ns laser ablation of amorphous SiSn in water at ambient conditions. Plasmas generated in the liquid by laser pulses are characterized by spatial confinement with very high pressure (GPa), which allowed the growth of the SiSn-NCs via kinetic pathways. We further illustrate that surface engineering by a direct-current atmospheric pressure microplasma is capable of tailoring the SiSn-NCs surface properties without the need for lengthy surfactants, resulting in room temperature photoluminescence (PL); the PL peak wavelength is red-shifted by more than 250 nm with respect to the PL peak wavelengths observed for comparable elemental silicon nanocrystals.


[Qualitative characteristics of Soviet kits for the radioimmunological determination of cortisol and progesterone in human blood serum].
Radioimmunoassays and kits of reagents based on them CORT-I-3H,STERON-K-125I, STERON-P-3H and STERON-P-125I intended for medical microanalysis, were studied. Their development and serial production were undertaken in the Institute of Bioorganic Chemistry, AS BSSR. The data obtained characterized the quality of the radioimmunoassays under study, long-term stability and reliability of the kits of reagents. A high specificity of antisera and correlation between the results of measurements and a degree of native blood serum dilution as well as the accuracy of the results obtained and sensitivity of the assays as a whole were demonstrated. The above properties of the radioimmunoassays made it possible to develop serial kits of reagents for determination of cortisol and progesterone concentration in the human blood serum, employed effectively in medical diagnosis of endocrine and other diseases. A long-term control over the reproducibility of parameters of calibration charts and the results of determination of the level of cortisol and progesterone in the pool blood serum of women showed a high reliability of the kits of reagents of different production lots within the time of their application observing instructions for use.


Are we justified in doing blood tests 'routinely' for all neurosurgical patients?
To ensure continuing patient care in a cost effective and efficient manner and to determine the importance of routine pre-op bloods in patients undergoing spine surgery, a retrospective audit of 170 patients was carried out in the Neurosurgery Department at Cork University Hospital. There were 94 males and 76 females. No test had less than 87.4% normal results. There were 17 (10.7%) abnormal haemoglobin levels, 13 (8.2%) abnormal white cell count levels, 14 (8.9%) abnormal creatinine levels and of sodium and potassium levels, 5 (3.2%) and 3 (2%) were abnormal respectively. Of the abnormal results, the majority fell close to reference range. 95% of the total cost incurred in performing the procedure was attributed to normal blood results. Abnormal blood results in this cohort of patients did not alter management. We conclude that routine blood tests, including coagulation screen, may not be necessary in healthy individuals undergoing elective spine surgery.


Multiple Meningioma in a Patient of Bipolar Disorder: The Dilemma of Detecting Structural Brain Lesions in the Backdrop of a Long Standing Psychiatric Illness.
Multiple meningioma often can be clinically silent and may present with only psychiatric symptoms. We report a case of 43-year-old, right handed woman with a 23 year history of long standing bipolar affective disorder, who presented with a mixed episode with psychotic symptoms which did not respond to usual treatment and was further complicated with a different set of symptomatology. MRI brain revealed multiple dural based mass lesions identified to be multiple meningiomas. Patient's symptoms improved after gamma knife stereotactic radiosurgery for the multiple meningioma. Our finding illustrates the need to assess for brain lesions in presence of atypical symptoms, along with unresponsiveness to traditional management with psychotropic medications in patients with bipolar affective disorders.


Transforming clients into experts-by-experience: A pilot in client participation in Dutch long-term elderly care homes inspectorate supervision.
As experts-by-experience, clients are thought to give specific input for and legitimacy to regulatory work. In this paper we track a 2017 pilot by the Dutch Health and Youth Care Inspectorate that aimed to use experiential knowledge in risk regulation through engaging with clients of long-term elderly care homes. Through an ethnographic inquiry we evaluate the design of this pilot. We find how the pilot transforms selected clients into experts-by-experience through training and site visits. In this transformation, clients attempt, and fail, to bring to the fore their definitions of quality and safety, negating their potentially specific contributions. Paradoxically, in their attempts to expose valid new knowledge on the quality of care, the pilot constructs the experts-by-experience in such a way that this knowledge is unlikely to be opened up. Concurrently, we find that in their attempts to have their input seen as valid, experts-by-experience downplay the value of their experiential knowledge. Thus, we show how dominating, legitimated interpretations of (knowledge about) quality of care resonate in experimental regulatory practices that explicitly try to move beyond them, emphasizing the need for a pragmatic and reflexive engagement with clients in the supervision of long-term elderly care.


Co-occurrence of brain tumours and demyelination of the central nervous system: coincidence or interrelation?
The co-occurrence of a brain tumour and demyelinating disease of the central nervous system (CNS) constitutes a rare clinical entity. We herein report the incidence of meningioma and CNS non-specific demyelination in a patient with a 6-year history of operated brain tumour (meningioma). Our case bolsters the argument that in at least some cases, the occurrence of a brain tumour could predispose to CNS non-specific demyelination.


Alloreactivity and association of human natural killer cells with the major histocompatibility complex.
All NK cells potentially lytic for autologous cells but not expressing self-major histocompatibility complex (MHC)-reactive receptors could be eliminated by a negative selection mechanism during ontogeny. This idea is based on the existence of a NK cell subset expressing a specific inhibitory receptor for allogeneic MHC alleles. As ancestral haplotypes of the MHC appear to define identical MHC haplotypes in unrelated individuals, unrelated individuals having the same ancestral haplotype should also have the same NK-defined allospecificities that have been shown to map to the human MHC. To test this prediction, multiple cell lines from unrelated individuals having the same ancestral haplotypes were tested for the NK-defined allospecificities. It was found that cells having the same ancestral haplotypes do have the same NK-defined specificities. Furthermore, the NK-defined phenotype of cells that possess two different ancestral haplotypes can be predicted from the NK-defined phenotypes of unrelated cells that are homozygous for the ancestral haplotypes concerned. Although the group 1 and 2 NK-defined allospecificities can be explained to some extent by HLA-C alleles, evidence is presented that additional genes may modify the phenotype conferred by HLA-C.


Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.
To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). Nonrandomized phase 1 clinical trial. Academic tertiary care hospital. Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. Patients were vaccinated on the thigh with irradiated autologous tumor cells admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 x 10(9) (range, 1.3 x 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3+ (>97%), being a mixture of CD4+ and CD8+ cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.


Bis(monoacylglycero)phosphate accumulation in macrophages induces intracellular cholesterol redistribution, attenuates liver-X receptor/ATP-Binding cassette transporter A1/ATP-binding cassette transporter G1 pathway, and impairs cholesterol efflux.
Endosomal signature phospholipid bis(monoacylglycero)phosphate (BMP) has been involved in the regulation of cellular cholesterol homeostasis. Accumulation of BMP is a hallmark of lipid storage disorders and was recently reported as a noticeable feature of oxidized low-density lipoprotein-laden macrophages. This study was designed to delineate the consequences of macrophage BMP accumulation on intracellular cholesterol distribution, metabolism, and efflux and to unravel the underlying molecular mechanisms. We have developed an experimental design to specifically increase BMP content in RAW 264.7 macrophages. After BMP accumulation, cell cholesterol distribution was markedly altered, despite no change in low-density lipoprotein uptake and hydrolysis, cholesterol esterification, or total cell cholesterol content. The expression of cholesterol-regulated genes sterol regulatory element-binding protein 2 and hydroxymethylglutaryl-coenzyme A reductase was decreased by 40%, indicative of an increase of endoplasmic reticulum-associated cholesterol. Cholesterol delivery to plasma membrane was reduced as evidenced by the 20% decrease of efflux by cyclodextrin. Functionally, BMP accumulation reduced cholesterol efflux to both apolipoprotein A1 and high-density lipoprotein by 40% and correlated with a 40% decrease in mRNA contents of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and liver-X receptor α and β. Foam cell formation induced by oxidized low-density lipoprotein exposure was exacerbated in BMP-enriched cells. The present work shows for the first time a strong functional link between BMP and cholesterol-regulating genes involved in both intracellular metabolism and efflux. We propose that accumulation of cellular BMP might contribute to the deregulation of cholesterol homeostasis in atheromatous macrophages.


Nonlinear response of summer temperature to Holocene insolation forcing in Alaska.
Regional climate responses to large-scale forcings, such as precessional changes in solar irradiation and increases in anthropogenic greenhouse gases, may be nonlinear as a result of complex interactions among earth system components. Such nonlinear behaviors constitute a major source of climate "surprises" with important socioeconomic and ecological implications. Paleorecords are key for elucidating patterns and mechanisms of nonlinear responses to radiative forcing, but their utility has been greatly limited by the paucity of quantitative temperature reconstructions. Here we present Holocene July temperature reconstructions on the basis of midge analysis of sediment cores from three Alaskan lakes. Results show that summer temperatures during 10,000-5,500 calibrated years (cal) B.P. were generally lower than modern and that peak summer temperatures around 5,000 were followed by a decreasing trend toward the present. These patterns stand in stark contrast with the trend of precessional insolation, which decreased by ∼10% from 10,000 y ago to the present. Cool summers before 5,500 cal B.P. coincided with extensive summer ice cover in the western Arctic Ocean, persistence of a positive phase of the Arctic Oscillation, predominantly La Niña-like conditions, and variation in the position of the Alaskan treeline. These results illustrate nonlinear responses of summer temperatures to Holocene insolation radiative forcing in the Alaskan sub-Arctic, possibly because of state changes in the Arctic Oscillation and El Niño-Southern Oscillation and associated land-atmosphere-ocean feedbacks.


Quality of life and gynecological cancers.
The quality of life is becoming more and more important for women after demolitive surgery for genital malignancies. A sample of 58 cases of genital malignancies are compared with 50 cases of benign neoplasms (fibroids) and their effects on sexuality, as a parameter of the quality of life, are studied and reported.


Electric-field-dependent spin polarization in GdN spin filter tunnel junctions.
Tunnel junctions incorporating GdN ferromagnetic semiconductor barriers show a spin polarization exceeding 90% and a high conductance. These devices show an unusual low-bias conductance peak arising from a strong bias-dependence of the spin polarization. This originates from a strong magneto-electric coupling within a double Schottky barrier formed with the NbN electrodes.