Dissemination of diabetes care guidelines: lessons learned from community health centers.
This study was conducted to evaluate the impact of a provider problem-based learning (PBL) intervention on screening for complications of diabetes in community health centers. A successive sampling design was used to compare selected standards of diabetes care delivered preintervention with the care delivered postintervention at 2 community health centers and 1 comparison centers. Two randomly assigned intervention sites received a PBL intervention focused on care guidelines for prevention of diabetes complications, with telephone follow-up over 12 months. Effects of the intervention were determined from an audit of 200 charts from each site. The odds of having a glycosylated hemoglobin test more than doubled from preintervention to postintervention, and the odds of having a foot examination more than tripled across centers. Measurement of creatinine and glycosylated hemoglobin were associated; the odds of having one test tripled when the other had been measured. Rates for documentation of patient education were significantly lower at the intervention site where free patient education booklets were distributed. Improvements in diabetes care were not consistent among community health centers. Interventions involving system and policy changes may be more effective in implementing and sustaining improvements than just provider education.


Risk of cancer in relatives of patients with myotonic dystrophy: a population-based cohort study.
Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted. DM was identified using the National Danish Patient Registry and results of genetic testing. Information on cancer was obtained from the Danish Cancer Registry. A population-based cohort of 5 757 565 individuals with at least one relative was established using the Danish Family Relations Database based on kinship links in the Danish Civil Registration System. Familial aggregation of cancer was evaluated by (incidence) rate ratios (RRs) comparing the rate of cancer amongst relatives of patients with DM from 1977 to 2010 (exposed) with the rate of cancer amongst persons with a relative of the same type but without DM (non-exposed). In first-degree relatives of individuals with DM the adjusted RR of cancer was 0.89 (95% confidence interval 0.71-1.12) overall, and in stratified analyses 0.68 (0.37-1.12) before age 50 and 0.96 (0.74-1.23) at age 50 or older. The present study does not support an increased risk of cancer in non-DM relatives of DM patients suggesting that cancer and DM are associated through derived effects of the DM genotype.


Enhancing resiliency and promoting prosocial behavior among Tanzanian primary-school students: A school-based intervention.
Children in Sub-Saharan Africa are living under chronic adversity due to poverty, serious health issues, physical and sexual abuse, and armed conflicts. These highly stressful conditions have deleterious effects on their mental health and socio-emotional adjustment. Since many children lack adequate access to mental health care, culturally adapted school-based resiliency programs could provide a resource to scaffold their development and promote their mental health. This study evaluated the efficacy of a universal school-based intervention in enhancing the resiliency of Tanzanian primary school children and cultivating prosocial behaviors. A total of 183 students from grades 4 to 6 were randomly assigned to either the 16-session "ERSAE-Stress-Prosocial (ESPS)" structured intervention or to a Social Study curriculum (SS) active control group. The original ESPS program was adapted by Tanzanians mental health professionals who modified the program based on local idioms of distress and indigenous practices. Students' resilience was evaluated before, after and 8 months following the intervention by assessing social difficulties, hyperactivity, somatization, level of anxiety, prosocial behaviors and school functioning as well as academic achievements and disciplinary problems. There was significant improvement on all outcome measures for the ESPS group compared to the control group post-intervention and at the 8-month follow up. The ESPS intervention was equally effective on most measures for students experiencing different adversity levels. The results indicate that a culturally adapted universal school-based intervention can be effective in enhancing Tanzanian students' resiliency and promoting prosocial behaviors. Should these results be replicated and found enduring, the modified ESPS could be a valuable mental health-promoting intervention in other low-income countries.


Characterization of senescence-associated protease activities involved in the efficient protein remobilization during leaf senescence of winter oilseed rape.
Oilseed rape (Brassica napus L.) is a crop plant characterized by a poor nitrogen (N) use efficiency that is mainly due to low N remobilization efficiency during the sequential leaf senescence of the vegetative stage. As a high leaf N remobilization efficiency was strongly linked to a high remobilization of proteins during leaf senescence of rapeseed, our objective was to identify senescence-associated protease activities implicated in the protein degradation. To reach this goal, leaf senescence processes and protease activities were investigated in a mature leaf becoming senescent in plants subjected to ample or low nitrate supply. The characterization of protease activities was performed by using in vitro analysis of RuBisCO degradation with or without inhibitors of specific protease classes followed by a protease activity profiling using activity-dependent probes. As expected, the mature leaf became senescent regardless of the nitrate treatment, and nitrate limitation enhanced the senescence processes associated with an enhanced degradation of soluble proteins. The characterization of protease activities revealed that: (i) aspartic proteases and the proteasome were active during senescence regardless of nitrate supply, and (ii) the activities of serine proteases and particularly cysteine proteases (Papain-like Cys proteases and vacuolar processing enzymes) increased when protein remobilization associated with senescence was accelerated by nitrate limitation. Short statement: Serine and particularly cysteine proteases (both PLCPs and VPEs) seem to play a crucial role in the efficient protein remobilization when leaf senescence of oilseed rape was accelerated by nitrate limitation.


The Home Literacy Environment as a Predictor of the Early Literacy Development of Children at Family-Risk of Dyslexia.
The home literacy environment (HLE) predicts language and reading development in typically developing children; relatively little is known about its association with literacy development in children at family-risk of dyslexia. We assessed the HLE at age 4 years, precursor literacy skills at age 5, and literacy outcomes at age 6, in a sample of children at family-risk of dyslexia (n = 116) and children with no known risk (n = 72). Developmental relationships between the HLE and literacy were comparable between the groups; an additional effect of storybook exposure on phoneme awareness was observed in the family-risk group only. The effects of socioeconomic status on literacy were partially mediated by variations in the HLE; in turn, effects of the HLE on literacy were mediated by precursor skills (oral language, phoneme awareness, and emergent decoding) in both groups. Findings are discussed in terms of possible gene-environment correlation mechanisms underpinning atypical literacy development.


A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit β5i.
Inhibition of the immunoproteasome subunit β5i alleviates autoimmune diseases in preclinical studies and represents a promising new anti-inflammatory therapy. However, the lack of structural data on the human immunoproteasome still hampers drug design. Here, we systematically determined the potency of seven α' β' epoxyketone inhibitors with varying N-caps and P3-stereochemistry for mouse/human β5c/β5i and found pronounced differences in their subunit and species selectivity. Using X-ray crystallography, the compounds were analyzed for their modes of binding to chimeric yeast proteasomes that incorporate key parts of human β5c, human β5i or mouse β5i and the neighboring β6 subunit. The structural data reveal exceptional conformations for the most selective human β5i inhibitors and highlight subtle structural differences as the major reason for the observed species selectivity. Altogether, the presented results validate the humanized yeast proteasome as a powerful tool for structure-based development of β5i inhibitors with potential clinical applications.


LC-MS-MS Analysis of Brodifacoum Isomers in Rat Tissue.
Brodifacoum (BDF) is a second-generation anticoagulant rodenticide structurally related to warfarin but containing two chiral centers. Highly stable, BDF can contaminate food and water supplies causing accidental poisoning of humans and nontarget animals. To determine the distribution of BDF isomers in serum and tissues, a quantitative method was developed and validated according to FDA guidelines based on high-performance liquid chromatography-tandem mass spectrometry. A single liquid-liquid extraction step provided recoveries exceeding 93%. Reversed-phase chromatographic separations required <6 min, and quantitative analysis utilized a triple-quadrupole mass spectrometer equipped with negative ion electrospray and selected reaction monitoring. The standard curve had a linear regression coefficient of 0.999 and intra- and inter-assay variations of <10%. The chromatographic method enabled the resolution and measurement of pairs of BDF diastereomers in commercial materials as well as in rat tissues. This method is suitable for measuring BDF exposure as well as basic science studies of the distribution and elimination of BDF diastereomers to various tissues.


Infarct-induced chronic heart failure increases bidirectional protein movement across the alveolocapillary barrier.
Chronic heart failure (CHF) is associated with adaptive structural changes at the alveolocapillary barrier that may be associated with altered protein permeability. Bidirectional protein movement across the barrier was studied in anesthetized rats with infarct-induced CHF by following (125)I-labeled albumin ((125)I-albumin) flux into the alveoli and the leakage of surfactant protein (SP)-B from the alveoli into the circulation. Three groups were studied: controls [0% left ventricular (LV) infarction], moderate infarct (25-45% LV infarction), and large infarct (>46% LV infarction). Wet and dry lung weights increased in the large infarct group (both P < 0.001), consistent with increased lung water and solid lung tissue. (125)I-albumin flux increased across the endothelial (P < 0.001) and epithelial (P < 0.01) components of the alveolocapillary barrier in the large infarct group. Plasma SP-B increased 23% with moderate infarcts (P < 0.05) and 97% with large infarcts (P < 0.001), independent of alveolar levels. Lavage fluid immune cells (P < 0.01) and myeloperoxidase activity (P < 0.05) increased in the large infarct group, consistent with inflammation. Bidirectional protein movement across the alveolocapillary barrier is increased in CHF, and alveolar inflammation may contribute to this pathophysiological defect.


Hydrogen Atom Abstraction by Permanganate: Oxidations of Arylalkanes in Organic Solvents.
Oxidations of arylalkanes by (n)()Bu(4)NMnO(4) have been studied in toluene solvent: toluene, ethylbenzene, diphenylmethane, triphenylmethane, 9,10-dihydroanthracene, xanthene, and fluorene. Toluene is oxidized to benzoic acid and a small amount of benzaldehyde; other substrates give oxygenated and/or dehydrogenated products. The manganese product of all of the reactions is colloidal MnO(2). The kinetics of the reactions, monitored by UV/vis spectrometry, show that the initial reactions are first order in the concentrations of both (n)()Bu(4)NMnO(4) and substrate. No induction periods are observed. The same rate constants for toluene oxidation are observed in neat toluene and in o-dichlorobenzene solvent, within experimental errors. The presence of O(2) increases the rate of (n)()Bu(4)NMnO(4) disappearance. The reactions of toluene and dihydroanthracene exhibit primary isotope effects: k(C)()7(H)()8/k(C)()7(D)()8 = 6 (+/-1) at 45 degrees C and k(C)()14(H)()12/k(C)()14(D)()12 = 3.0 (+/-0.6) at 25 degrees C. The rates of oxidation of substituted toluenes show only small substituent effects. In the reactions of dihydroanthracene and fluorene, the MnO(2) product is consumed in a subsequent reaction that appears to form a charge-transfer complex. The rate-limiting step in all of the reactions is hydrogen atom transfer from the substrate to a permanganate oxo group. The enthalpies of activation for the different substrates are directly proportional to the DeltaH degrees for the hydrogen atom transfer step, as is typical of organic radical reactions. The ability of permanganate to abstract a hydrogen atom is explained on the basis of its ability to form an 80 +/- 3 kcal/mol bond to H(*), as calculated from a thermochemical cycle. (This bond strength is slightly lower than given in earlier calculations.) Rates of H(*) abstraction by (n)()Bu(4)NMnO(4) correlate with rates of abstraction by oxygen radicals.


Nitrogen use in the United States from 1961-2000 and potential future trends.
Nitrogen inputs to the US from human activity doubled between 1961 and 1997, with most of the increase in the 1960s and 1970s. The largest increase was in use of inorganic N fertilizer, but emissions of NOx from fossil-fuel combustion also increased substantially. In 1961, N fixation in agricultural systems was the largest single source of reactive N in the US. By 1997, even though N fixation had increased, fertilizer use and NOx emissions had increased more rapidly and were both larger inputs. In both 1961 and 1997, two thirds of reactive N inputs were denitrified or stored in soils and biota, while one third was exported. The largest export was in riverine flux to coastal oceans, followed by export in food and feeds, and atmospheric advection to the oceans. The consumption of meat protein is a major driver behind N use in agriculture in the US Without change in diet or agricultural practices, fertilizer use will increase over next 30 years, and fluxes to coastal oceans may increase by another 30%. However, substantial reductions are possible.


Facebook surveillance of former romantic partners: associations with postbreakup recovery and personal growth.
Previous research has found that continuing offline contact with an ex-romantic partner following a breakup may disrupt emotional recovery. The present study examined whether continuing online contact with an ex-partner through remaining Facebook friends and/or engaging in surveillance of the ex-partner's Facebook page inhibited postbreakup adjustment and growth above and beyond offline contact. Analysis of the data provided by 464 participants revealed that Facebook surveillance was associated with greater current distress over the breakup, more negative feelings, sexual desire, and longing for the ex-partner, and lower personal growth. Participants who remained Facebook friends with the ex-partner, relative to those who did not remain Facebook friends, reported less negative feelings, sexual desire, and longing for the former partner, but lower personal growth. All of these results emerged after controlling for offline contact, personality traits, and characteristics of the former relationship and breakup that tend to predict postbreakup adjustment. Overall, these findings suggest that exposure to an ex-partner through Facebook may obstruct the process of healing and moving on from a past relationship.


Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics.
Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000-2003. The last population-based assessment of TSS was 1986. Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) from 2000-2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases. Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual) were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32-0.77), 0.69 (0.39-1.16), and 0.32 (0.12-0.67), respectively. Women 13-24 years had the highest incidence at 1.41 (0.63-2.61). No increase in incidence was observed from 2000-2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively]. TSS incidence remained stable across our surveillance period of 2000-2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has been consistently used but likely results in a substantial underestimation of the total TSS disease burden.


Speech and language therapists' approaches to communication intervention with children and adults with profound and multiple learning disability.
People with profound intellectual and multiple disabilities (PMLD) have communication impairments as one defining characteristic. To explore speech and language therapists' (SLTs) decision making in communication interventions for people with PMLD, in terms of the intervention approaches used, the factors informing the decisions to use specific interventions and the extent to which the rationales underpinning these decisions related to the components of evidence based practice (EBP), namely empirical evidence, clinical experience and client/carer views and values. A questionnaire on communication assessment and intervention for people with PMLD was sent to SLTs in the UK to elicit information on: the communication intervention approaches they used; their rationales for their intervention choices; their use of published evidence to inform decision making. Intensive interaction and objects of reference were the communication interventions most often used with people with PMLD, with some differences between children and adults evident. Rationales provided conformed somewhat to the EBP framework though extension of the existing framework and addition of practical and organizational considerations led to a revised typology of rationale for decision making. Rationales most frequently related to the empowerment, development and behavioural preferences of the person with PMLD. Empirical research evidence was seldom mentioned by SLTs as informing intervention decision making leading to very diverse practice. There is a need for further research on the effectiveness of commonly used but under-evaluated interventions. There is also a need to alert SLTs to the evidence base supporting other approaches, particularly switch-based, cause and effect approaches.


Origin and segregation of cranial placodes in Xenopus laevis.
Cranial placodes are local thickenings of the vertebrate head ectoderm that contribute to the paired sense organs (olfactory epithelium, lens, inner ear, lateral line), cranial ganglia and the adenohypophysis. Here we use tissue grafting and dye injections to generated fate maps of the dorsal cranial part of the non-neural ectoderm for Xenopus embryos between neural plate and early tailbud stages. We show that all placodes arise from a crescent-shaped area located around the anterior neural plate, the pre-placodal ectoderm. In agreement with proposed roles of Six1 and Pax genes in the specification of a panplacodal primordium and different placodal areas, respectively, we show that Six1 is expressed uniformly throughout most of the pre-placodal ectoderm, while Pax6, Pax3, Pax8 and Pax2 each are confined to specific subregions encompassing the precursors of different subsets of placodes. However, the precursors of the vagal epibranchial and posterior lateral line placodes, which arise from the posteriormost pre-placodal ectoderm, upregulate Six1 and Pax8/Pax2 only at tailbud stages. Whereas our fate map suggests that regions of origin for different placodes overlap extensively with each other and with other ectodermal fates at neural plate stages, analysis of co-labeled placodes reveals that the actual degree of overlap is much smaller. Time lapse imaging of the pre-placodal ectoderm at single cell resolution demonstrates that no directed, large-scale cell rearrangements occur, when the pre-placodal region segregates into distinct placodes at subsequent stages. Our results indicate that individuation of placodes from the pre-placodal ectoderm does not involve large-scale cell sorting in Xenopus.


Preoperative functional mapping for rolandic brain tumor surgery: comparison of navigated transcranial magnetic stimulation to direct cortical stimulation.
Transcranial magnetic stimulation (TMS) is the only noninvasive method for presurgical stimulation mapping of cortical function. Recent technical advancements have significantly increased the focality and usability of the method. To compare the accuracy of a 3-dimensional magnetic resonance imaging-navigated TMS system (nTMS) with the gold standard of direct cortical stimulation (DCS). The primary motor areas of 20 patients with rolandic tumors were mapped preoperatively with nTMS at 110% of the individual resting motor threshold. Intraoperative DCS was available from 17 patients. The stimulus locations eliciting the largest electromyographic response in the target muscles ("hotspots") were determined for both methods. The nTMS and DCS hotspots were located on the same gyrus in all cases. The mean ± SEM distance between the nTMS and DCS hotspots was 7.83 ± 1.18 mm for the abductor pollicis brevis (APB) muscle (n = 15) and 7.07 ± 0.88 mm for the tibialis anterior muscle (n = 8). When a low number of DCS stimulations was performed, the distance between the nTMS and DCS hotspots increased substantially (r = -0.86 for APB). After the exclusion of the cases with < 15 DCS APB responses, the mean ± SEM distance between the hotspots was only 4.70 ± 1.09 mm for APB (n = 8). Peritumoral mapping of the motor cortex by nTMS agreed well with the gold standard of DCS. Thus, nTMS is a reliable tool for preoperative mapping of motor function.


Use of record-linkage to handle non-response and improve alcohol consumption estimates in health survey data: a study protocol.
Reliable estimates of health-related behaviours, such as levels of alcohol consumption in the population, are required to formulate and evaluate policies. National surveys provide such data; validity depends on generalisability, but this is threatened by declining response levels. Attempts to address bias arising from non-response are typically limited to survey weights based on sociodemographic characteristics, which do not capture differential health and related behaviours within categories. This project aims to explore and address non-response bias in health surveys with a focus on alcohol consumption. The Scottish Health Surveys (SHeS) aim to provide estimates representative of the Scottish population living in private households. Survey data of consenting participants (92% of the achieved sample) have been record-linked to routine hospital admission (Scottish Morbidity Records (SMR)) and mortality (from National Records of Scotland (NRS)) data for surveys conducted in 1995, 1998, 2003, 2008, 2009 and 2010 (total adult sample size around 40 000), with maximum follow-up of 16 years. Also available are census information and SMR/NRS data for the general population. Comparisons of alcohol-related mortality and hospital admission rates in the linked SHeS-SMR/NRS with those in the general population will be made. Survey data will be augmented by quantification of differences to refine alcohol consumption estimates through the application of multiple imputation or inverse probability weighting. The resulting corrected estimates of population alcohol consumption will enable superior policy evaluation. An advanced weighting procedure will be developed for wider use. Ethics approval for SHeS has been given by the National Health Service (NHS) Multi-Centre Research Ethics Committee and use of linked data has been approved by the Privacy Advisory Committee to the Board of NHS National Services Scotland and Registrar General. Funding has been granted by the MRC. The outputs will include four or five public health and statistical methodological international journal and conference papers. Public health. Addiction: health policy; mental health.


Multipole Dirichlet-to-Neumann map method for photonic crystals with complex unit cells.
The periodicity of photonic crystals can be utilized to develop efficient numerical methods for analyzing light waves propagating in these structures. The Dirichlet-to-Neumann (DtN) operator of a unit cell maps the wave field on the boundary of the unit cell to its normal derivative, and it can be used to reduce the computation to the edges of the unit cells. For two-dimensional photonic crystals with complex unit cells, each containing a number of possibly different circular cylinders, we develop an efficient multipole method for constructing the DtN maps. The DtN maps are used to calculate the transmission and reflection spectra for finite photonic crystals with complex unit cells.


[Acute otitis media: Diagnosis and treatment].
Acute otitis media (AOM) is one of the most common causes of medical visit and antimicrobial use in children. A rationale management approach requires a thorough clinical exam and updated knowledge on local patterns of microorganisms involved and antimicrobial susceptibility profiles. Clinical diagnosis should be performed with pneumatic otoscopy. The most common microorganism causing AOM in Santiago, Chile according to local studies are Streptococcus pneumoniae (40%o), non-capsulated Haemophilus influenzae (29%), Streptococcus pyogenes (7%) and Moraxella catarrhalis (4%). S. pneumoniae has acquired resistance to penicillin in the last decade, resistance that has been extrapolated to other (b lactams such as amoxicillin, reason why broader spectrum antimicrobials are routinely prescribed. Clinical practice has consistently shown although that the great majority of children receiving amoxicillin at a dose of 80-100 mg/kg/day resolve their AOM. Recent studies from our group have demonstrated that resistance to penicillin can not be extrapolated to amoxicillin. In vitro high level resistance to penicillin vs amoxicillin is 18%> vs 0.5%. Based on this data, our current recommendation for AOM is amoxicillin 80 mg/kg/day, q 12 hours for 10 days in infants and for 5-7 days in children > 2 years of age who have not had an episode within the previous month. For amoxicillin failures, amoxicillin + (b lactam inhibitor or a second generation cephalosporin are recommended, especially in areas with a high prevalence of (b lactam producing H. influenzae and M. catarrhalis. Treatment of children with AOM universally require appropriate follow-up in order to comply with the proposed algorithm.


The effect of orally administered epigallocatechin-3-gallate on ligature-induced periodontitis in rats.
Epigallocatechin-3-gallate (EGCG) is known for its beneficial properties, including anti-inflammatory and anti-oxidative activities. Recently, reports have suggested that EGCG plays a pivotal role in regulating cytokine expression and osteoclastic activity. In the present study, we investigated whether orally administered EGCG has a therapeutic effect on ligature-induced periodontitis. Forty-eight Sprague-Dawley rats were treated with EGCG or phosphate-buffered saline. Periodontitis was induced by tying a ligature for 7 d. After removing ligation, EGCG (200 mg/kg) or phosphate-buffered saline was administered via oral gavage on a daily basis. Rats were killed after 1, 2 and 4 wk of administration. Histologic and histomorphometric analyses, tartrate resistant acid phosphatase staining and immunohistochemistry were carried out. In the control group, bone loss did not recover even after the causative factor of periodontitis was eliminated. On the other hand, distance from cemento-enamel junction to alveolar bone crest, long junctional epithelium and collagen destruction were reduced in the EGCG group. Decreased interleukin (IL)-6 expression was shown from the early stage of EGCG administration, followed by reduced tumor necrosis factor (TNF) expression at week 4 EGCG group. The CT area showed a higher decrease of IL-6 expression between the control and EGCG group than alveolar bone area. Downregulation of TNF and IL-6 expression led to a decrease in osteoclast number and activity, which resulted in reduced bone loss. Systemic administration of EGCG could have a therapeutic effect on damaged periodontal tissue. Inhibited cytokine expression, including TNF and IL-6 is responsible for the reduction in osteoclast formation, osteoclastic activity and collagen destruction.


Rapid method for sensitive screening of oligosaccharide epitopes in the lipooligosaccharide from Campylobacter jejuni strains isolated from Guillain-Barré syndrome and Miller Fisher syndrome patients.
Campylobacter jejuni lipooligosaccharide (LOS) can trigger Guillain-Barré syndrome (GBS) due to its similarity to human gangliosides. Rapid and accurate structural elucidation of the LOS glycan of a strain isolated from a GBS patient could help physicians determine the spectrum of anti-ganglioside antibodies likely to be found and therefore provide valuable assistance in establishing an appropriate course of treatment. The ability of implemented mass spectrometry-based approaches in a clinical setting has been limited by the laborious and time-consuming nature of the protocols, typically 3 to 4 days, used to prepare LOS. In order to improve the analytical throughput, microwave-assisted enzymatic digestion was investigated. In this study, the bacterial cells were suspended in 50 microl of 20 mM ammonium acetate buffer containing DNase and RNase and treated by direct microwave irradiation for 3 min. Then, proteinase K was added and the samples were again microwaved. The intact LOS samples were analyzed using electrophoresis-assisted open-tubular liquid chromatography-mass spectrometry. The reliability of the rapid, high-throughput technique was demonstrated through analysis of LOS glycans from 73 C. jejuni strains. The structure was elucidated using material from a single colony. The total time for sample preparation and MS analysis is less than 60 min.


Evolutionary origin and radiation of the avian-adapted non-motile salmonellae.
Multilocus enzyme electrophoresis was employed to estimate chromosomal genotypic diversity and relationships among 131 isolates of the non-motile Salmonella biotypes Gallinarum and Pullorum (serotype 1, 9, 12:-:-) that cause fowl typhoid and pullorum disease, respectively. Thirteen electrophoretic types (ETs), marking clones, were distinguished, and construction of a neighbour-joining phylogenetic tree revealed three lineages: one consisted of five ETs of Gallinarum, a second included seven ETs of Pullorum, and a third was represented by a single ET (Ga/Pu 1) that is intermediate between those of the other two lineages in both multilocus enzyme genotype and biochemical properties. Enzyme genotype analysis and comparative nucleotide sequencing of the phase 1 flagellin gene (fliC), the hook-associated protein 1 gene (flgK), and the 6-phosphogluconate dehydrogenase gene (gnd) identified serotype Enteritidis (1, 9, 12:g, m:-) as a close relative of the non-motile salmonellae. In most strains of biotype Gallinarum, the fliC gene is complete, intact and identical in sequence to that of Enteritidis, but isolates of three ETs had a stop codon at position 495. The fliC sequences of the ETs of Pullorum differed from that of Enteritidis in having non-synonymous changes in either two or three codons and a synonymous change in one codon. The sharing of distinctive alleles at three metabolic enzyme loci and a stop codon in flgK indicates that the non-motile salmonellae are monophyletic and that their most recent common ancestor was non-motile. Since diverging from that ancestor, the Pullorum lineage has evolved more rapidly than the Gallinarum and Ga/Pu 1 lineages.


Experience, Perceptions, and Recommendations Concerning COVID-19-Related Clinical Research Adjustments.
During the COVID-19 public health emergency, the FDA and NIH altered clinical trial requirements to protect participants and manage study conduct. Given their detailed knowledge of research protocols and regular contact with patients, clinicians, and sponsors, clinical research professionals offer important perspectives on these changes. We developed and distributed an anonymous survey assessing COVID-19-related clinical trial adjustment experiences, perceptions, and recommendations to Clinical Research Office personnel at the Harold C. Simmons Comprehensive Cancer Center. Responses were compared using the Fisher exact test. A total of 94 of 109 contacted research personnel (87%) responded. Among these individuals, 58% had >5 years' professional experience in clinical research, and 56% had personal experience with a COVID-19-related change. Respondents perceived that these changes had a positive impact on patient safety; treatment efficacy; patient and staff experience; and communication with patients, investigators, and sponsors. More than 90% felt that positive changes should be continued after COVID-19. For remote consent, telehealth, therapy shipment, off-site diagnostics, and remote monitoring, individuals with personal experience with the specific change and individuals with >5 years' professional experience were numerically more likely to recommend continuing the adjustment, and these differences were significant for telehealth (P=.04) and therapy shipment (P=.02). Clinical research professionals perceive that COVID-19-related clinical trial adjustments positively impact multiple aspects of study conduct. Those with greatest experience-both specific to COVID-19-related changes and more generally-are more likely to recommend that these adjustments continue in the future.


Patient and visit characteristics associated with opportunistic preventive services delivery.
This study's purpose was to identify patient and visit characteristics associated with the use of illness visits as opportunities for the delivery of preventive services and to determine if time is allocated differently during illness visits that make use of these opportunities. Research nurses directly observed the delivery of preventive services during consecutive patient visits on 2 separate days in the offices of 138 family physicians. Data on patient eligibility for preventive services were collected by medical record review. Time use during patient visits was categorized using the Davis Observation Code (DOC). Patient characteristics, visit characteristics, and time use were compared during illness visits in which at least one service recommended by the US Preventive Services Task Force was delivered to eligible patients, compared with illness visits during which no recommended preventive services were delivered. Preventive services were delivered during 32% of 3547 illness visits. Adults, overweight patients, those who smoke or drink alcohol, new patients, and patients with fewer visits in the past year were more likely to receive preventive services. Patient request was also associated with increased delivery of preventive services. The presence of another family member, visits for an acute illness, and the prescription of a drug were associated with a decreased likelihood of a patient's receiving preventive services. When preventive services were delivered during illness visits, less time was spent on chatting, procedures, and physical examination, and more time was spent on history-taking. Family physicians take greater advantage of opportunities for the delivery of preventive services during the illness visits of high-risk patients. The results of our study suggest strategies that could be used to expand the opportunistic delivery of preventive services to other patients and types of visits.


quit4u: the effectiveness of combining behavioural support, pharmacotherapy and financial incentives to support smoking cessation.
The 'quit4u' stop smoking service (SSS) was developed by National Health Service (NHS) Tayside for smokers in deprived areas of Dundee (UK). quit4u combined behavioural support and pharmacotherapy with financial incentives for each week that participants remained quit. A quasi-experimental study was undertaken with smokers using quit4u between 2009 and 2011 compared with smokers using SSSs in the rest of Scotland. The outcome measures were: number of quit attempts; quit rates at 1, 3 and 12 months; cost-effectiveness. Mechanisms of change were explored through quantitative and qualitative research that explored the views and experiences of service users and professionals involved in quit4u. The number of quit attempts made using SSSs in deprived areas of NHS Tayside increased by 44% between 2007 and 2010. quit4u had significantly higher quit rates at 1 month (49.9% versus 33.7%), 3 months (30.7% versus 14.2%) and 12 months (9.3% versus 6.5%) compared with similar smokers using other SSSs. The incremental cost per quitter was £2296. A combination of elements kept clients engaged and supported quit attempts: carbon monoxide (CO) tests, financial incentives, high-quality pharmacy support, rolling groups and greater varenicline use. quit4u may provide an effective and cost-effective model for engaging and supporting smokers in deprived areas to quit.


Unnecessary workup of asymptomatic neonates in the era of group B streptococcus prophylaxis.
Asymptomatic term neonates born to mothers who are Group B Streptococcus (GBS) unknown or GBS positive but "inadequately" treated prior to delivery do not require invasive laboratory evaluation. We conducted a retrospective cohort study of mother/baby dyads born from January 1, 2005 until September 30, 2007 at the Medical College of Georgia. Their current protocol is to obtain a Complete Blood Count with Differential (CBC with D), Blood Culture (BC), and C-reactive protein (CRP) after birth. Mother/baby dyads (n = 242) that met inclusion criteria were reviewed. Of these 242 babies 25 (10%) were started on antibiotics after the initial lab values were known. None of the blood cultures were positive and the CRP's were normal. The 2002 GBS guidelines call for laboratory evaluation of "at-risk" neonates, but the workup of these babies is not only costly, it does not provide any advantage over old fashioned clinical observation for the evaluation and treatment of early onset GBS sepsis.


Effects of functional electrical stimulation in rehabilitation with hemiparesis patients.
Cerebrovascular accident is a focal neurological deficiency occurring suddenly and lasting for more than 24 hours. The purpose of our work is to determine the role of the functional electrical simulation (FES) in the rehabilitation of patients with hemiparesis, which occurred as a consequence of a cerebrovascular accident. This study includes the analysis of two groups of 40 patients with hemiparesis (20 patients with deep hemiparesis and 20 patients with light hemiparesis), a control group which was only treated with kinesiotherapy and a tested group which was treated with kinesiotherapy and functional electrical stimulation. Both groups of patients were analyzed in respect to their sex and age. Additional analysis of the walking function was completed in accordance with the BI and RAP index. The analysis of the basic demographical data demonstrated that there is no significant difference between the control and tested group. The patients of both groups are equal in respect of age and sex. After 4 weeks of rehabilitation of patients with deep and light hemiparesis there were no statistically significant differences between the groups after evaluation by the BI index. However, a statistically significant difference was noted between the groups by the RAP index among patients with deep hemiparesis. After 8 weeks of rehabilitation the group of patients who were treated with kinesiotherapy and functional electrical stimulation showed better statistically significant results of rehabilitation in respect to the control group with both the BI index and the RAP index (p<0,001). In conclusion, we can state that the patients in rehabilitation after a cerebrovascular accident require rehabilitation longer than 4 weeks. Walking rehabilitation after stroke is faster and more successful if we used functional electrical stimulation, in combination with kinesiotherapy, in patients with disabled extremities.


Multimodal integration for the representation of space in the posterior parietal cortex.
The posterior parietal cortex has long been considered an 'association' area that combines information from different sensory modalities to form a cognitive representation of space. However, until recently little has been known about the neural mechanisms responsible for this important cognitive process. Recent experiments from the author's laboratory indicate that visual, somatosensory, auditory and vestibular signals are combined in areas LIP and 7a of the posterior parietal cortex. The integration of these signals can represent the locations of stimuli with respect to the observer and within the environment. Area MSTd combines visual motion signals, similar to those generated during an observer's movement through the environment, with eye-movement and vestibular signals. This integration appears to play a role in specifying the path on which the observer is moving. All three cortical areas combine different modalities into common spatial frames by using a gain-field mechanism. The spatial representations in areas LIP and 7a appear to be important for specifying the locations of targets for actions such as eye movements or reaching; the spatial representation within area MSTd appears to be important for navigation and the perceptual stability of motion signals.


A multi-paradigm framework to assess the impacts of climate change on end-use energy demand.
Projecting the long-term trends in energy demand is an increasingly complex endeavor due to the uncertain emerging changes in factors such as climate and policy. The existing energy-economy paradigms used to characterize the long-term trends in the energy sector do not adequately account for climate variability and change. In this paper, we propose a multi-paradigm framework for estimating the climate sensitivity of end-use energy demand that can easily be integrated with the existing energy-economy models. To illustrate the applicability of our proposed framework, we used the energy demand and climate data in the state of Indiana to train a Bayesian predictive model. We then leveraged the end-use demand trends as well as downscaled future climate scenarios to generate probabilistic estimates of the future end-use demand for space cooling, space heating and water heating, at the individual household and building level, in the residential and commercial sectors. Our results indicated that the residential load is much more sensitive to climate variability and change than the commercial load. Moreover, since the largest fraction of the residential energy demand in Indiana is attributed to heating, future warming scenarios could lead to reduced end-use demand due to lower space heating and water heating needs. In the commercial sector, the overall energy demand is expected to increase under the future warming scenarios. This is because the increased cooling load during hotter summer months will likely outpace the reduced heating load during the more temperate winter months.


Social relationships, sleep quality, and interleukin-6 in aging women.
This study examined the interplay of social engagement, sleep quality, and plasma levels of interleukin-6 (IL-6) in a sample of aging women (n = 74, aged 61-90, M age = 73.4). Social engagement was assessed by questionnaire, sleep was assessed by using the NightCap in-home sleep monitoring system and the Pittsburgh Sleep Quality Index, and blood samples were obtained for analysis of plasma levels of IL-6. Regarding subjective assessment, poorer sleep (higher scores on the Pittsburgh Sleep Quality Index) was associated with lower positive social relations scores. Multivariate regression analyses showed that lower levels of plasma IL-6 were predicted by greater sleep efficiency (P < 0.001), measured objectively and by more positive social relations (P < 0.05). A significant interaction showed that women with the highest IL-6 levels were those with both poor sleep efficiency and poor social relations (P < 0.05). However, those with low sleep efficiency but compensating good relationships as well as women with poor relationships but compensating high sleep efficiency had IL-6 levels comparable to those with the protective influences of both good social ties and good sleep.


Motion perception under mesopic vision.
Mesopic and scotopic vision extend over an illuminance range of 106. The goal of the present study was to determine the effect of decreasing light level on the underlying motion mechanism that integrates spatiotemporally separated motion signals. To accomplish this, we took advantage of the phenomenon of visual motion priming, in which the perceived direction of a directionally ambiguous test stimulus is influenced by the directional movement of a preceding priming stimulus. After terminating a drifting priming stimulus, a 180° phase-shifted grating was presented as a test stimulus. The priming and test stimuli were separately presented to the central and peripheral retinas, respectively. The participants judged the perceived direction of this test stimulus at various light levels from photopic to scotopic levels. We found that the effects of motion priming disappeared over 1 log unit of mesopic light levels. When the test stimulus was presented before the offset of the priming stimulus to compensate for the temporal delay in the rod pathway or when both stimuli were presented at the same location in the periphery, a motion-priming effect appeared at mesopic light levels. These results suggest that different temporal characteristics between the cone pathway and rod pathway disturb the function of the putative motion mechanism responsible for the spatiotemporal integration of motion signals, which leads to specific modulation of motion perception over a wide range of mesopic vision.


Mode area scaling with multi-trench rod-type fibers.
We propose a novel all-solid rod-type fiber structure that presents a cylindrical symmetry and low refractive-index contrasts. Effectively single-mode propagation for the fundamental mode is ensured thanks to resonant couplings between Higher Order Modes (HOMs) and cladding modes. Numerical simulations demonstrate the possibility of achieving a fundamental mode effective area as large as 5000 µm² at a wavelength of 1.06 μm in fibers ensuring a high leakage loss ratio (>100) between the HOMs and the fundamental mode while keeping the fundamental mode leakage losses at a level lower than 0.2dB/m. Further scaling to an effective area of 12,200 µm2 at 1.06 μm in an effectively single-mode fiber is also presented by exploiting the power delocalization of several HOMs on top of the high-leakage loss filtering.


Interaction of primary human endometrial cells with Neisseria gonorrhoeae expressing green fluorescent protein.
Infection of the endometrium by Neisseria gonorrhoeae is a pivotal stage in the development of pelvic inflammatory disease in women. An ex vivo model of cultures of primary human endometrial cells was developed to study gonococcal-host cell interactions. To facilitate these studies, gonococci were transformed with a hybrid shuttle vector containing the gfp gene from Aequoria victoria, encoding the green fluorescent protein (GFP), to produce intrinsically fluorescent bacteria. The model demonstrated that both pili and Opa proteins were important for both mediating gonococcal interactions with endometrial cells and inducing the secretion of pro-inflammatory cytokines and chemokines. Pil+ gonococci showed high levels of adherence and invasion, regardless of Opa expression, which was associated with increased secretion of IL-8 chemokine and reduced secretion of IL-6 cytokine. Gonococcal challenge also caused increased secretion of TNF-alpha cytokine, but this did not correlate with expression of pili or Opa, suggesting that release of components from non-adherent bacteria may be involved in TNF-alpha induction. Thus, the use of cultured primary endometrial cells, together with gonococci expressing green fluorescent protein, has the potential to extend significantly our knowledge, at the molecular level, of the role of this important human pathogen in the immunobiology of pelvic inflammatory disease.


Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker.
The immunoreactive protein for the tissue inhibitor of the metalloproteinase (TIMP)-1 and -2 as well as for the matrix metalloproteinase (MMP)-2 and -9 was quantified from the sera/plasma of 90 lung cancer patients and 20 control subjects with enzyme linked immunoassays (ELISA) using specific monoclonal antibodies. Free MMP-2 and that bound to the inhibitor, the MMP-2/TIMP-2 complex were measured separately using different ELISAs. For the detection of MMP-9, TIMP-1 and TIMP-2, the total protein was measured to quantify both free and complex forms. Serum protein levels for TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex differed significantly in patients with lung cancer when compared to controls. TIMP-1 levels were found to be higher in lung cancer than in controls, whereas TIMP-2 and MMP-2/TIMP-2 complex levels were lower in lung cancer than in the sera of the control subjects. High TIMP-1 (> 300 ng/ml) or MMP-9 (> 30 ng/ml) correlated to poor cumulative survival in lung cancer patients (log rank P < 0.05). High TIMP-1 indicated a poor prognosis, especially in squamous cell cancer and in NSCLC patients with stage III: 66% and 70%, respectively, of the patients with low TIMP-l serum levels survived for more than one year, when only 25% and 20%, respectively, of the patients with high serum levels for TIMP-1 protein survived at that time. 56% of lung cancer patients with a plasma MMP-9 level < 30 ng/ml survived for 12 months when only 31% of the lung cancer patients with high MMP-9 plasma levels survived for more than one year. Also this difference was significant (log rank analysis, P < 0.05). Our results suggest that the factors of the metalloproteinase system might be important in lung cancer progression. TIMP-1 as well as MMP-9 could serve as prognostic markers, and their values could be investigated in the follow-up of lung cancer patients when selecting patients for systemic chemotherapy or other treatment modalities.


Motor function and white matter connectivity in children cooled for neonatal encephalopathy.
Therapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischaemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in children aged 6-8 years treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched typically developing controls. Correlations between total motor scores and diffusion properties in major white matter tracts were assessed in 33 cases and 36 controls. In cases, significant correlations (FDR-corrected P < 0.05) were found in the anterior thalamic radiation bilaterally (left: r = 0.513; right: r = 0.488), the cingulate gyrus part of the left cingulum (r = 0.588), the hippocampal part of the left cingulum (r = 0.541), and the inferior fronto-occipital fasciculus bilaterally (left: r = 0.445; right: r = 0.494). No significant correlations were found in controls. We then constructed structural connectivity networks, for 22 cases and 32 controls, in which nodes represent brain regions and edges were determined by probabilistic tractography and weighted by fractional anisotropy. Analysis of whole-brain network metrics revealed correlations (FDR-corrected P < 0.05), in cases, between total motor scores and average node strength (r = 0.571), local efficiency (r = 0.664), global efficiency (r = 0.677), clustering coefficient (r = 0.608), and characteristic path length (r = -0.652). No significant correlations were found in controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores (P = 0.0109) as well as for balance (P = 0.0245) and manual dexterity (P = 0.0233) domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. The subnetwork associated with total motor scores was highly left-lateralised. These findings demonstrate an association between impaired motor function and brain organisation in school-age children treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.


Incidence of acute urinary tract infection in young women and use of male condoms with and without nonoxynol-9 spermicides.
Acute urinary tract infection is one of the most common infections seen in primary care. We conducted a nested case-control study among a cohort of 519 women, ages 15-29 years, enrolled in a contraceptive acceptability study to examine whether recent use of male condoms increases urinary tract infection risk. One hundred sixty-five incident urinary tract infections were identified during 12-month follow-up periods in a cohort study that was conducted between 1996 and 1999. After exclusions for urinary tract infection recurrences, pregnancy, antibiotic use, diabetes, diaphragm/cervical cap use, or urinary tract abnormalities, there were 100 cases and 200 controls. Compared with women not using barrier methods (and after adjustment for age, urinary tract infection history, hormonal method use, and frequency of sex) the odds ratio (OR) for any reported use of condoms coated with spermicide (Nonoxynol-9) in the previous 30 days was 2.8 (95% [confidence interval] CI = 1.2-6.5). The OR was 11.5 (95% CI = 2.5-53) for exclusive Nonoxynol-9-coated condom use. The OR for exclusive use of non-Nonoxynol-9-coated condoms was 7.4 (95% CI = 1.6-35). In this study, use of male condoms was associated with increased urinary tract infection risk; the largest risk was associated with exclusive condom use and use of Nonoxynol-9-coated condoms.


Exploring the patient experience of remote hypertension management in Scotland during COVID-19: a qualitative study.
The aim of this study was to understand how patients experienced hypertension management, with or without blood pressure (BP) telemonitoring, during the COVID-19 pandemic. This qualitative study conducted between April and November 2022 consisted of 43 semistructured telephone interviews (23 men and 20 women) from 6 primary care practices in one area of Scotland. From the views of 25 participants with experience of using the Connect Me telemonitoring service and 18 participants without such experience, 5 themes were developed. These were: (1) navigating access to services. There were challenges to gaining timely and/or in-person access to services and a reluctance to attend clinical settings because participants were aware of their increased risk of contracting the COVID-19 virus. (2) Adapting National Health Service services. All six practices had adapted care provision in response to potential COVID-19 transmission; however, these adaptations disrupted routine management of in-person primary care hypertension, diabetes and/or asthma checks. (3) Telemonitoring feedback. Telemonitoring reduced the need to attend in-person primary care practices and supported access to remote healthcare monitoring and feedback. (4) Self-management. Many non-telemonitoring participants were motivated to use self-management strategies to track their BP using home monitoring equipment. Also, participants were empowered to self-manage lifestyle and hypertension medication. (5) Experience of having COVID-19. Some participants contracting the COVID-19 virus experienced an immediate increase in their BP while a few experienced ongoing increased BP readings. The COVID-19 pandemic disrupted routine in-person care for patients with hypertension. Both telemonitoring and some non-telemonitoring patients were motivated to self-manage hypertension, including self-adjusting medication; however, only those with access to telemonitoring had increased access to hypertension monitoring and feedback. BP telemonitoring permitted routine care to continue for participants in this study and may offer a service useful in pandemic proofing hypertension healthcare in the future.


Transnational cultural ecologies: evolving challenges for nurses in Canada.
Canada is experiencing an evolving cultural ecology as new arrivals of immigrants now realize opportunities for sustaining familiar ties with home countries through advancing technologies and travel. Those arriving will have diverse experiences and preferences, many with opportunities for meeting their health needs elsewhere. For those less privileged, options for health care and health enabling resources are more limited as existing health systems continue to give preference to a dominant culture based on a European heritage-even though, progressively, Canadian society becomes more diverse in its cultural makeup. We as nurses and others engaged in health care systems need to consider our own acculturation processes as we adapt to the changes happening in our society. Systemic approaches to cultural competency in health care need to be considered that enable nurses and other health care providers to be adaptive and resilient in a transnational world.


Proton efflux from rat skeletal muscle in vivo: changes in hypertension.
1. An analysis of the recovery kinetics of intracellular pH and phosphocreatine concentration after exercise in skeletal muscle was developed to calculate the rate of proton efflux in vivo. 2. Recovery of rat leg muscle pH after sciatic nerve stimulation was faster in spontaneously hypertensive rats than in Wistar-Kyoto controls (both n = 5). 3. Analysis of these data showed that the rate of proton efflux depends on intracellular pH, being greater at lower pH. 4. The early rate of proton efflux was greater in spontaneously hypertensive rats [measured over the first 0.8 min, 12.5 mmol min-1 kg-1 (SEM 1.8) in spontaneously hypertensive rats compared with 7.6 mmol min-1 kg-1 (SEM 0.4) in Wistar-Kyoto rats, P less than 0.05], even though pH at the start of recovery was higher [6.30 (SEM 0.03) in spontaneously hypertensive rats compared with 6.17 (SEM 0.01) in Wistar-Kyoto rats, P less than 0.01]. 5. This novel analysis provides a quantitative estimate of the rate of proton efflux in vivo, and demonstrates directly that this is increased in spontaneously hypertensive rats, as has previously been inferred from pH changes during exercise and studies of cultured muscle cells in vitro.


Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety.
Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A(1) and A(2A) receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A(2A) (ADORA2A) and DRD(2) (DRD2) receptors. Healthy male and female individuals (n=102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3'-flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.


Acinic Cell Carcinoma of the Parotid Gland in Children and Adolescents.
Acinic cell carcinoma of the parotid gland is a rare low-grade malignant neoplasm. Data on children are sparse. For the present study, the database of a tertiary pediatric medical center was reviewed for all patients with parotid gland acinic cell carcinoma diagnosed and treated between 2004 and 2013. Clinical, histologic, treatment, and outcome parameters were collected from the medical files. Four patients were identified, 3 female and 1 male, aged 13.5 to 18 years (median 15.7) at diagnosis. One patient had a family history of parotid tumor and 1 of hypothyroidism/hyperthyroidism. Two patients had L-thyroxin-treated Hashimoto thyroiditis, and 1 had a thyroid nodule. All presented with a localized parotid mass and negative lymph nodes. Treatment consisted of partial parotidectomy, with no damage to the facial nerve. Histology confirmed the diagnosis of acinic cell carcinoma with low proliferation rate (Ki67 immunostaining 1% to 8%). No evidence of disease was found on any patient with a median follow-up at 83 months (range, 32 to 93 mo) from presentation. In our experience, the prognosis of pediatric parotid gland acinic cell carcinoma is good, and surgery alone is sufficient for treatment of early stage tumors. This is the first report of findings of a family history of thyroid disease and/or thyroid abnormalities in patients with parotid gland acinic cell carcinoma.


Xenopus laevis Stromal cell-derived factor 1: conservation of structure and function during vertebrate development.
Transmembrane signaling of the CXC chemokine stromal cell-derived factor-1 (SDF-1) is mediated by CXCR4, a G protein-coupled receptor initially identified in leukocytes and shown to serve as a coreceptor for the entry of HIV into lymphocytes. Characterization of SDF-1- and CXCR4-deficient mice has revealed that SDF-1 and CXCR4 are of vital developmental importance. To study the role of the SDF-1/CXCR4-chemokine/receptor system as a regulator of vertebrate development, we isolated and characterized a cDNA encoding SDF-1 of the lower vertebrate Xenopus laevis (xSDF-1). Recombinant xSDF-1 was produced in insect cells, purified, and functionally characterized. Although xSDF-1 is only 64-66% identical with its mammalian counterparts, it is indistinguishable from human (h)SDF-1alpha in terms of activating both X. laevis CXCR4 and hCXCR4. Thus, both xSDF-1 and hSDF-1alpha promoted CXCR4-mediated activation of heterotrimeric G(i2) in a cell-free system and induced release of intracellular calcium ions in and chemotaxis of intact lymphoblastic cells. Analysis of the time course of xSDF-1 mRNA expression during Xenopus embryogenesis revealed a tightly coordinated regulation of xSDF-1 and X. laevis CXCR4. xSDF-1 mRNA was specifically detected in the developing CNS, incipient sensory organs, and the embryonic heart. In Xenopus, CXCR4 mRNA appears to be absent from the heart anlage, but present in neural crest cells. This observation suggests that xSDF-1 expressed in the heart anlage may attract cardiac neural crest cells expressing CXCR4 to migrate to the primordial heart to regulate both septation of the cardiac outflow tract and differentiation of the myocardium during early heart development.


An unusual cause of ventilatory failure in motor neurone disease.
A patient previously diagnosed with motor neurone disease (MND) and gastrostomy-fed was under surveillance for ventilatory decline via our respiratory centre. At a planned review she was found to be hypercapnic, which would usually prompt an offer of non-invasive ventilation for home use. However, she was alkalotic and not acidotic as we might expect. Her serum potassium was checked urgently and confirmed as low. It was established that the community team had prescribed a feeding regime with insufficient potassium. Correction of hypokalaemia resolved her ventilatory failure. This case demonstrates the importance of co-ordinated care in the management of patients with MND.


The semantic pathfinder: using an authoring metaphor for generic multimedia indexing.
This paper presents the semantic pathfinder architecture for generic indexing of multimedia archives. The semantic pathfinder extracts semantic concepts from video by exploring different paths through three consecutive analysis steps, which we derive from the observation that produced video is the result of an authoring-driven process. We exploit this authoring metaphor for machine-driven understanding. The pathfinder starts with the content analysis step. In this analysis step, we follow a data-driven approach of indexing semantics. The style analysis step is the second analysis step. Here, we tackle the indexing problem by viewing a video from the perspective of production. Finally, in the context analysis step, we view semantics in context. The virtue of the semantic pathfinder is its ability to learn the best path of analysis steps on a per-concept basis. To show the generality of this novel indexing approach, we develop detectors for a lexicon of 32 concepts and we evaluate the semantic pathfinder against the 2004 NIST TRECVID video retrieval benchmark, using a news archive of 64 hours. Top ranking performance in the semantic concept detection task indicates the merit of the semantic pathfinder for generic indexing of multimedia archives.


Urinary incontinence and risk of functional decline in older women: data from the Norwegian HUNT-study.
The main objective of the present study was to determine whether UI is an independent predictor of ADL decline and IADL decline in elderly women. We also aimed to find out whether incontinent subjects were at higher risk of needing help from formal home care or home nursing care during 11 year follow-up. A prospective cohort study conducted as part of the North-Trøndelag Health Study 2 and 3. Women aged 70-80 years when participating in the HUNT 2 study, who also participated in the HUNT 3 study, were included in this study. Analyses on self-reported urinary incontinence at baseline and functional decline during a11-year period were performed for incontinent and continent subjects. Baseline prevalence of urinary incontinence was 24%. At on average eleven year follow up, logistic regression analysis showed a significant association between incontinence and decline in activities of daily living (ADL) (OR =2.37, 95% CI =1.01-5.58) (P=0.04). No association between urinary incontinence and instrumental activities of daily living (IADL) in incontinent women compared with continent women was found (OR=1.18, CI=.75-1.86) (P=.46). Data were adjusted for ADL, IADL and co morbid conditions at baseline. No significant differences in need of more help from formal home care and home nursing care between continent and incontinent women were found after 11 years of follow-up. Urinary incontinence is an important factor associated with functional decline in women aged 70-80 years living in their own homes. At eleven years of follow up, no significant differences in need of more help from formal home care and home nursing care between continent and incontinent women were found.


Financial Abuse of Older Adults: Screening, Prevention, and Interventions by Primary Care Providers.
The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry. Prim Care Companion. 2023;25(3):22f03434. Author affiliations are listed at the end of this article.


Protective altruistic phlebotomy: hereditary haemochromatosis presenting as hepatocellular carcinoma in a non-cirrhotic 83-year-old man.
Hereditary haemochromatosis is a multisystem disorder of iron metabolism. Hepatic manifestations include hepatomegaly, cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma is almost always preceded by cirrhosis. We present a case of an 83-year-old man without history of liver disease or iron overload who presented with abdominal pain. Workup revealed mildly elevated transaminases, ferritin of 3996 and a solitary liver tumour. Biopsy was consistent with hepatocellular carcinoma in a background of haemosiderosis without cirrhosis. He was diagnosed with hereditary haemochromatosis and hepatocellular carcinoma. He underwent a partial hepatectomy and was started on routine phlebotomy and surveillance imaging. He has improved and has not had signs of recurrence or new complications of haemochromatosis. We suggest a possible reason for his unique and late presentation.


Dynamics of bacterial and fungal communities associated with eggshells during incubation.
Microorganisms are closely associated with eggs and may play a determinant role in embryo survival. Yet, the majority of studies focusing on this association relied on culture-based methodology, eventually leading to a skewed assessment of microbial communities. By targeting the 16S rRNA gene and internal transcribed spacer (ITS) region, we, respectively, described bacterial and fungal communities on eggshells of the homing pigeon Columba livia. We explored their structure, abundance, and composition. Firstly, we showed that sampling technique affected the outcome of the results. While broadly used, the egg swabbing procedure led to a lower DNA extraction efficiency and provided different profiles of bacterial communities than those based on crushed eggshell pieces. Secondly, we observed shifts in bacterial and fungal communities during incubation. At late incubation, bacterial communities showed a reduction in diversity, while their abundance increased, possibly due to the competitive advantage of some species. When compared to their bacterial counterparts, fungal communities also decreased in diversity at late incubation. In that case, however, the decline was associated with a diminution of their overall abundance. Conclusively, our results showed that although incubation might inhibit microbial growth when compared to unincubated eggs, we observed the selective growth of specific bacterial species during incubation. Moreover, we showed that fungi are a substantial component of the microbial communities associated with eggshells and require further investigations in avian ecology. Identifying the functional roles of these microorganisms is likely to provide news insights into the evolutionary strategies that control embryo survival. We aimed to describe the dynamics of bacterial and fungal communities on homing pigeon eggshell surfaces. We investigated these communities at early and late incubation stages.


Parameter identifiability and estimation of HIV/AIDS dynamic models.
We use a technique from engineering (Xia and Moog, in IEEE Trans. Autom. Contr. 48(2):330-336, 2003; Jeffrey and Xia, in Tan, W.Y., Wu, H. (Eds.), Deterministic and Stochastic Models of AIDS Epidemics and HIV Infections with Intervention, 2005) to investigate the algebraic identifiability of a popular three-dimensional HIV/AIDS dynamic model containing six unknown parameters. We find that not all six parameters in the model can be identified if only the viral load is measured, instead only four parameters and the product of two parameters (N and lambda) are identifiable. We introduce the concepts of an identification function and an identification equation and propose the multiple time point (MTP) method to form the identification function which is an alternative to the previously developed higher-order derivative (HOD) method (Xia and Moog, in IEEE Trans. Autom. Contr. 48(2):330-336, 2003; Jeffrey and Xia, in Tan, W.Y., Wu, H. (Eds.), Deterministic and Stochastic Models of AIDS Epidemics and HIV Infections with Intervention, 2005). We show that the newly proposed MTP method has advantages over the HOD method in the practical implementation. We also discuss the effect of the initial values of state variables on the identifiability of unknown parameters. We conclude that the initial values of output (observable) variables are part of the data that can be used to estimate the unknown parameters, but the identifiability of unknown parameters is not affected by these initial values if the exact initial values are measured with error. These noisy initial values only increase the estimation error of the unknown parameters. However, having the initial values of the latent (unobservable) state variables exactly known may help to identify more parameters. In order to validate the identifiability results, simulation studies are performed to estimate the unknown parameters and initial values from simulated noisy data. We also apply the proposed methods to a clinical data set to estimate HIV dynamic parameters. Although we have developed the identifiability methods based on an HIV dynamic model, the proposed methodologies are generally applicable to any ordinary differential equation systems.


Gerstmann-Sträussler-Scheinker disease showing beta-protein type cerebellar and cerebral amyloid angiopathy.
Cerebral amyloid angiopathy is observed in several brain degenerative disorders, but this pathological condition has received little attention in Gerstmann-Sträussler-Scheinker disease (GSS). We report a 69-year-old man who showed the cardinal features of GSS together with typical and extensive congophilic angiopathy. Immunohistochemical studies revealed that the vast majority of the amyloid plaques present in the brain of this patient were consistently labeled by anti-prion protein (PrP) antibody. Double immunostaining disclosed many additional beta-protein immunoreactive plaque-like lesions, including a special type of "hybrid" plaque with colocalization of PrP and beta-protein (beta-PrP). The vascular amyloid deposits seen in both the cerebellum and cerebrum were immunoreactive only to anti-beta-protein antibody. It seems likely that the extensive deposition of beta-protein amyloid (including brain vascular amyloidosis) seen in this and other similar cases is part of pathology of GSS, although the possibility that this finding is due to ageing or concomitant Alzheimer's disease cannot be completely ruled out.


Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ.
Previous study has suggested that the FABP5-PPARγ-signalling transduction pathway gradually replaces the androgen receptor activated pathway in promoting malignant progression of castration-resistant prostate cancer (CRPC) cells. To interfere with this newly discovered FABP5-related signalling pathway, we have produced a highly efficient recombinant FABP5 inhibitor, named dmrFABP5. Treatment with dmrFABP5 significantly supressed the proliferation, migration, invasion and colony formation of the highly malignant prostate cancer cells PC3-M in vitro. To test dmrFABP5's suppressive effect in CRPC, the human PC3-M cells were implanted orthotopically into the prostate gland of immunosuppressed mice to produce tumours. These mice were then treated with dmrFABP5 and produced a highly significant reduction of 100% in metastatic rate and a highly significant reduction of 13-fold in the average size of primary tumours. Immunocytochemial staining showed that the staining intensity of dmrFABP5 treated tumours was reduced by 67%. When tested in vitro, dmrFABP5 suppressed the cancer cells by blocking fatty acid stimulation of PPARγ, and thereby prevented it activating down-stream cancer-promoting or inhibiting cancer-suppressing genes. Our results show that the FABP5 inhibitor dmrFABP5 is a novel molecule for treatment of experimental CRPC and its inhibitory effect is much greater than that produced by SB-FI-26 reported in our previous work.


PAGE analysis of the heteroduplexes formed between PCR-amplified 16S rRNA genes: estimation of sequence similarity and rDNA complexity.
Analysis of the 16S rRNA genes retrieved directly from different environments has proven to be a powerful tool that has greatly expanded our knowledge of microbial diversity and phylogeny. It is shown here that sequence similarity between 80 and 100% among 16S rDNAs can be estimated by the electrophoretic migration of their heteroduplexes. This was measured by hybridization and electrophoresis in polyacrylamide gels of the product obtained after PCR amplification of almost the entire 16S rRNA gene from different bacterial species. These heteroduplexes were also observed after amplification of samples containing DNA from two or more bacterial species and a procedure was applied to identify reliably heteroduplexes among the amplification products. The electrophoretic migration of the heteroduplexes observed after PCR was used to detect the presence of 16S rDNAs with different sequences in DNA extracted from both a mixture of two bacterial species and samples containing a natural bacterial community.


Electrogenic and electroneutral HCO3-secretion by guinea pig gallbladder epithelium: discriminatory abilities of Cl- channel blockers.
The specificity of Cl- channel blockers (including 5-nitro-2-(3-phenylpropylamino-)benzoic acid (NPPB), diphenylamine-carboxylic acid and 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid (MPTC)) was studied in guinea pig gallbladder. This epithelium performs electroneutral HCO3- secretion, due to cell-to-lumen exit by Cl-/HCO3- exchange. At high intracellular cyclic AMP levels [produced by prostaglandin E1, (PGE1)], secretion turns electrogenic, secondary to induction of apical membrane Cl- and HCO3- conductances. Part of HCO3- secretion remains Cl(-)-dependent. Microelectrode, voltage-clamp and pH-stat techniques were used to determine membrane potentials, short-circuit current (Isc) and secretory HCO3- fluxes. With one exception, effective agents (concentration range 10(-5)-10(-4) M, luminal bath) including NPPB and diphenylamine-carboxylic acid inhibited secretory HCO3- fluxes in the presence and absence of PGE1 as well as PGE1-induced Isc. At 10(-4) M, inhibition of Isc was not attenuated by Cl- removal; however, NPPB effects were less at concentrations < 10(-4) M. MPTC (3 x 10(-5)-3 x 10(-4) M) only partly inhibited PGE1-induced Isc, was almost ineffective in Cl(-)-free solutions, and did not affect secretory HCO3- flux under any condition. Effects of NPPB and MPTC were distinct from those of the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone. This agent (10(-7)-10(-5) M), failed to discriminate between Cl(-)-dependent and -independent Isc. In control tissues, 10(-5) M carboyl cyanide p-trifluoromethoxy-phenylhydrazone practically abolished membrane potentials, whereas 10(-4) M NPPB produced no change.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiological, Risk Factors, Clinical, and Laboratory Features of Brucellosis in the Southwest of Iran within 2009-2015.
Brucellosis is a serious disease affecting many individuals in the world and in Iran. The aim of this study was to investigate the epidemiological and clinical features of patients diagnosed with brucellosis in Kohgilouyeh and Boyerahmad province, southwest of Iran. This retrospective descriptive-analytic study included all individuals diagnosed with brucellosis during 2009-2015. The clinical and epidemiological information were gathered from recorded data available in the health center of Kohgilouyeh and Boyerahmad province, the southwest of Iran. The total number of patients diagnosed with brucellosis during the study period was 658, of whom, 339 (51.5%) were males. A total of 541 (82.2%) patients resided in rural and tribal areas, and the others lived in urban regions. The mean age of diagnosis was 39.59 ± 17.28 years and the most prevalent age groups were 31-50 (277, 42.1%) and 11-30 (178, 27.1%)-year olds. The most affected groups were housekeeper women (229, 34.8%) and ranchers (152, 23.1%). The relationship between jobs and disease was significant (P < 0.001). Transmission through either suspected dairy products (582, 88.4%) or close contact with infected livestock (537, 81.6%) comprised the most common routes of brucellosis dissemination. The clinical presentation was acute in the majority (581, 88.3%) of the patients. The highest titer for both wright and Coombs wright tests was 1:320. The most frequently administrated drugs were doxycycline and streptomycin (183, 27.8%). The most commonly observed clinical symptom was bone pain (477, 72.5%). Arthritis (12, 1.8%) comprised the most frequent drug-associated complication. Either relapse or treatment failure was recorded collectively in four (0.6%) patients. Due to the prevalence of the disease in the nomadic areas, timely detection and control of the disease is essential. Furthermore, livestock vaccination along with educating farmers and physicians about brucellosis can be helpful.


What Patients Know About Services to Help Manage Chronic Diseases and Medications: Findings from Focus Groups on Medication Therapy Management.
Managing and treating patients with multiple chronic conditions presents challenges on many levels. Pharmacist-delivered medication therapy management (MTM) services, mandated as part of the Medicare Part D drug benefit, are designed to help patients manage their chronic conditions and medications. To identify factors that influence patient understanding and use of MTM services and potential strategies to educate individuals about MTM. Participants who had at least 2 chronic conditions, were taking 2 or more prescription medications, and were aged 18 years or older were recruited from community-based settings to participate in focus groups. The focus groups aimed to identify participants' perceptions and use of MTM services, barriers and facilitators to utilization, and medication problems. Participants were asked to complete a 14-item health care questionnaire and view a brief, 3-minute video introducing the topic of MTM before the group discussion. The health care questionnaire data were analyzed in Microsoft Excel. The focus group responses were transcribed and entered into the computer program ATLAS.ti for thematic analysis. Two independent reviewers qualitatively coded the discussion question responses; a third reviewer investigated discrepancies and facilitated consensus among the reviewers. Participants (N = 27) were mostly female (70.4%), college educated (62.9%), and had Medicare insurance (81.5%). Seven themes were identified: (1) new proposed names for MTM, (2) mechanisms to gain interest in and to promote the value of MTM, (3) familiarity with MTM, (4) pharmacists' training and expertise in MTM, (5) experience with MTM, (6) reasons for nonparticipation in MTM, and (7) preferred method to learn about MTM. Participants did not understand the term "medication therapy management" and felt the interpretation of "therapy"' differed between health care professionals and the public. Some participants used MTM services to learn about appropriate use of their medications, while others were unsure about their eligibility, associated costs, and how to access the services. Participants had limited pharmaceutical knowledge but felt pharmacist-provided MTM services were helpful. Participants were unfamiliar with pharmacists' skills and training. Participants' experiences with MTM services ranged from disregarding the invitation to participate to having pharmacists identify drug-drug interactions. Reasons for nonparticipation in MTM services included being unaware of their eligibility, failing to read excessive information from insurance companies, and being uncertain of the identity of the telephone caller. Preferred methods for learning more about MTM services included the Internet, e-mail, information availability at physician's office, and television advertisements. These results suggest that the lay public remains largely unaware of MTM services and that the term "MTM" is not well understood. Clearly, tailored public health campaigns and patient engagement strategies are needed to promote MTM in chronic disease management, pharmacists as respected providers, and the importance of the prescriber-MTM pharmacist collaborative relationship in managing medications for patients with multiple chronic conditions. Grant funding from SinfoniaRx to Taylor, Axon, Campbell, Fair, and Warholak was used to help conduct this project. Boesen is employed by SinfoniaRx. The other authors have nothing to disclose. This original research was presented as a poster at the Academy of Managed Care Pharmacy 27th Annual Meeting and Expo; April 7-10, 2015; San Diego, CA.


Defective B cell responses in the absence of SH2D1A.
More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A(-/-) mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A(-/-) B cell functions were impaired. Using the adoptive cotransfer of B lymphocytes from hapten-primed SH2D1A(-/-) mice with CD4(+) T cells from primed wt mice into irradiated wt mice provided evidence that signal transduction events controlled by SH2D1A are essential for B cell activities resulting in antigen specific IgG production. Defects in naive SH2D1A(-/-) B cells became evident upon cotransfer with non-primed wt CD4(+) cells into Rag2(-/-) recipients. Thus, both defective T and B cells exist in the absence of SH2D1A, which may explain the progressive dysgammaglobulinemia in a subset of X-linked lympho-proliferative disease patients without involvement of Epstein-Barr virus.


Wnt-dependent epithelial transitions drive pharyngeal pouch formation.
The pharyngeal pouches, which form by budding of the foregut endoderm, are essential for segmentation of the vertebrate face. To date, the cellular mechanism and segmental nature of such budding have remained elusive. Here, we find that Wnt11r and Wnt4a from the head mesoderm and ectoderm, respectively, play distinct roles in the segmental formation of pouches in zebrafish. Time-lapse microscopy, combined with mutant and tissue-specific transgenic experiments, reveal requirements of Wnt signaling in two phases of endodermal epithelial transitions. Initially, Wnt11r and Rac1 destabilize the endodermal epithelium to promote the lateral movement of pouch-forming cells. Next, Wnt4a and Cdc42 signaling induce the rearrangement of maturing pouch cells into bilayers through junctional localization of the Alcama immunoglobulin-domain protein, which functions to restabilize adherens junctions. We propose that this dynamic control of epithelial morphology by Wnt signaling may be a common theme for the budding of organ anlagen from the endoderm.


Interventions to improve teamwork and communications among healthcare staff.
Concern over the frequency of unintended harm to patients has focused attention on the importance of teamwork and communication in avoiding errors. This has led to experiments with teamwork training programmes for clinical staff, mostly based on aviation models. These are widely assumed to be effective in improving patient safety, but the extent to which this assumption is justified by evidence remains unclear. A systematic literature review on the effects of teamwork training for clinical staff was performed. Information was sought on outcomes including staff attitudes, teamwork skills, technical performance, efficiency and clinical outcomes. Of 1036 relevant abstracts identified, 14 articles were analysed in detail: four randomized trials and ten non-randomized studies. Overall study quality was poor, with particular problems over blinding, subjective measures and Hawthorne effects. Few studies reported on every outcome category. Most reported improved staff attitudes, and six of eight reported significantly better teamwork after training. Five of eight studies reported improved technical performance, improved efficiency or reduced errors. Three studies reported evidence of clinical benefit, but this was modest or of borderline significance in each case. Studies with a stronger intervention were more likely to report benefits than those providing less training. None of the randomized trials found evidence of technical or clinical benefit. The evidence for technical or clinical benefit from teamwork training in medicine is weak. There is some evidence of benefit from studies with more intensive training programmes, but better quality research and cost-benefit analysis are needed.


Plasticity of feeding behavior in the opisthobranch mollusc Navanax.
Several forms of plasticity of feeding behavior were investigated in Navanax. Navanax is a gastropod mollusc which lacks a radula, and ingests prey with suction caused by rapid pharyngeal expansion. Feeding is little affected by handling or posture and is resistant to the noxious stimulus of cutting through the body wall. Feeding is affected by arousal, as shown by a decrease in latency following initial exposure to food. The feeding response also habituates, as shown by an increase in latency when feeding responses are elicited without allowing animals to engulf food. The latency increase is not likely to be due to motor fatigue, since it can be partially reversed by dishabituation with an alternate prey species. Continued feeding causes satiation, as shown by increased feeding latencies and eventual cessation of feeding after a mean weight gain of 42.0% of initial animal weight (N = 12). Another form of plasticity occurs when Navanax are presented with food too large to swallow whole. Navanax either cease to respond after a few presentations, perhaps due to habituation, or maintain suction on the partially swallowed prey for an extended period of time. During extended sucks, the more deeply ingested portions are digested.


Kinetic energy of Throughfall in subtropical forests of SE China - effects of tree canopy structure, functional traits, and biodiversity.
Throughfall kinetic energy (TKE) plays an important role in soil erosion in forests. We studied TKE as a function of biodiversity, functional diversity as well as structural stand variables in a secondary subtropical broad-leaved forest in the Gutianshan National Nature Reserve (GNNR) in south-east China, a biodiversity hotspot in the northern hemisphere with more than 250 woody species present. Using a mixed model approach we could identify significant effects of all these variables on TKE: TKE increased with rarefied tree species richness and decreased with increasing proportion of needle-leaved species and increasing leaf area index (LAI). Furthermore, for average rainfall amounts TKE was decreasing with tree canopy height whereas for high rainfall amounts this was not the case. The spatial pattern of throughfall was stable across several rain events. The temporal variation of TKE decreased with rainfall intensity and increased with tree diversity. Our results show that more diverse forest stands over the season have to cope with higher cumulative raindrop energy than less diverse stands. However, the kinetic energy (KE) of one single raindrop is less predictable in diverse stands since the variability in KE is higher. This paper is the first to contribute to the understanding of the ecosystem function of soil erosion prevention in diverse subtropical forests.


Inhibitory effects of procyanidin B(2) dimer on lipid-laden macrophage formation.
A proteomic analysis of procyanidin B(2) isolated from cocoa against oxidized low-density lipoprotein-induced lipid-laden macrophage formation was performed. Of approximately 400 detected proteins, 12 were differentially expressed as a result of B(2) treatment. They were subsequently identified by liquid chromatography-electrospray ionization-tandem mass spectrometry and the SWISS-PROT database. Further reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that B(2) strongly inhibited arachidonic acid inflammatory reactions, apoptosis, and their coupled mitogen-activated protein kinase and NF-kappaB pathways. To highlight proteins or genes with similar expressed patterns and similarly biological function induced by B(2) in lipid-laden macrophages, a cluster and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. The data were mapped to multiple pathways. Further validation of the bioinformatic results revealed that activation of Wnt signaling may contribute to the cardioprotection of B(2). The differentially expressed genes and proteins mentioned above induced by B(2) are through regulating nuclear transcription factors, activating peroxisome proliferator-activated receptor-gamma and inhibiting AP-1 mRNA expressions. These in vitro data help to interpret the beneficial effects of B(2) in reducing the risk of atherosclerosis after consumption of flavonoid-rich foods. Many differentially expressed genes induced by B(2) help to uncover novel targets and may help to target disease interactions in atherosclerosis in the future.


[Nonalcoholic steatohepatitis in children].
Nonalcoholic steatohepatitis (NASH) occurs not only in adults but also in children. NASH is diagnosed in obese children with increased aminotranspherases, characteristic ultrasonography and typical percutneous liver biopsy (fat vacuoles in hepatocytes, different stages of inflammation with or without liver fibrosis) when other possible causes of steatosis are excluded. It is important to diagnose NASH and start the treatment as early as possible in order to prevent irreversible liver damage. The first line therapy consists of reduction of body weight by low-calorie diet and exercising. Ursodeoxycholic acid has been used as adjuvant therapy mainly in adults, and vitamin E also in children. We presented 5 cases with NASH (2 girls, 3 boys; age 11-15 years). All were obese and had increased transaminases, and ultrasonography and liver biopsy typical for NASH. With low-calorie diet in all our patients BMI declined, symptoms vanished and transaminases decreased (in two patients transaminases normalized).


Microbial biotechnology approaches to mitigating the deterioration of construction and heritage materials.
Microorganisms are the main engines of elemental cycling in this planet and therefore have a profound impact on both organic and mineral substrates. As such, past and present human-made structures and cultural heritage can be negatively affected by microbial activity. Processes such as bioweathering (rocks and minerals), biodeterioration (organic substrates) or biocorrosion (metals) participate to the degradation or structural damage of construction and heritage materials. This structural damage can cause major economic losses (e.g. replacement of cast-iron pipes in water distribution networks), and in the case of heritage materials, the entire loss of invaluable objects or monuments. Even though one can regard the influence of microbial activity on construction and heritage materials as negative, remarkably, the same metabolic pathways involved in degradation can be exploited to increase the stability of these materials.