Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.
Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions. Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience. Clinical data from Progesterone for the Treatment of Traumatic Brain Injury trial were available for all 74 patients represented in the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study (including 46 patients for whom the surrogate was interviewed due to the patient's cognitive status or death). No significant difference was observed regarding acceptance of general trial inclusion or acceptance of general exception from informed consent enrollment between participants with favorable neurological outcomes and those with unfavorable outcomes relative to initial injury. Agreement with personal enrollment in Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent, however, was significantly higher among participants with favorable outcomes compared to those with unfavorable outcomes (89% vs 59%, p = 0.003). There was also a statistically significant relationship between more severe initial injury and increased acceptance of personal exception from informed consent enrollment ( p = 0.040) or general exception from informed consent use ( p = 0.034) in Progesterone for the Treatment of Traumatic Brain Injury trial. Many individuals referenced personal experience as a basis for their attitudes, but these references were not used to support negative views. Patients and surrogates of patients with unfavorable clinical outcomes were somewhat less accepting of their own inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent than were patients or surrogates of patients with favorable clinical outcomes. These findings suggest a need to identify optimal strategies for communicating with patients and their surrogates regarding exception from informed consent enrollment when clinical outcomes are poor.


Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.
Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR.


Magnesium in kidney diseases. A review.
During the last decades the kidney has emerged as a key organ in the homeostasis of magnesium and disturbances of magnesium metabolism have been described in several renal diseases. Restoring body stores to normal levels should be one of the goals in the conservative treatment of end stage renal failure, since magnesium retention is thought to participate in uraemic toxicity. The kidney is also the target organ of many drugs and increased magnesium excretion can be observed either as an obligatory side effect or as a sign of nephrotoxicity. Magnesium depletion could participate in the vascular complications observed with such drugs. The significance of hypomagnesaemia in Bartter's syndrome remains obscure. Renal stone disease is frequently associated with a low urinary magnesium output, although the determinants of this abnormality are still not well understood.


Vegetarian and vegan diets: benefits and drawbacks.
Plant-based diets have become increasingly popular thanks to their purported health benefits and more recently for their positive environmental impact. Prospective studies suggest that consuming vegetarian diets is associated with a reduced risk of developing cardiovascular disease (CVD), diabetes, hypertension, dementia, and cancer. Data from randomized clinical trials have confirmed a protective effect of vegetarian diets for the prevention of diabetes and reductions in weight, blood pressure, glycosylated haemoglobin and low-density lipoprotein cholesterol, but to date, no data are available for cardiovascular event rates and cognitive impairment, and there are very limited data for cancer. Moreover, not all plant-based foods are equally healthy. Unhealthy vegetarian diets poor in specific nutrients (vitamin B12, iron, zinc, and calcium) and/or rich in highly processed and refined foods increase morbidity and mortality. Further mechanistic studies are desirable to understand whether the advantages of healthy, minimally processed vegetarian diets represent an all-or-nothing phenomenon and whether consuming primarily plant-based diets containing small quantities of animal products (e.g. pesco-vegetarian or Mediterranean diets) has beneficial, detrimental, or neutral effects on cardiometabolic health outcomes. Further, mechanistic studies are warranted to enhance our understanding about healthy plant-based food patterns and the biological mechanisms linking dietary factors, CVD, and other metabolic diseases.


Benefits of the National Dairy Council to the dairy processing industry.
The National Dairy Council and its affiliated units have had a vital role in presenting the nutritional qualities of US dairy products to a variety of audiences. Established in 1915, National Dairy Council has been the segment of the dairy industry that initiates and administers nutrition research, implements cutting-edge educational programs, and communicates about the nutritional merits of dairy products to educators, health professionals, consumers, and other important groups. The grassroots structure of National Dairy Council allows it to communicate these important messages at both the national and local levels.


Gold Nanoparticle Loaded Split-DNAzyme Probe for Amplified miRNA Detection in Living Cells.
A new class of intracellular nanoprobe, termed AuNP loaded split-DNAzyme probe, was developed to sense miRNA in living cells. Briefly, it consists of an AuNP and substrates hybridized with two half of split DNAzymes. In the absence of target miRNA, the split DNAzymes form an inactive DNAzyme motif with their substrate through partial paring at the end of each strand, and the fluorescence is quenched. Inside the cells, the target miRNA binds with both of the two half of split DNAzymes, forming the active secondary structure in the catalytic cores, which can cleave the substrates, resulting in the rupture of the substrate and recovery of the fluorescence. Meanwhile, the target is released and binds to another inactive DNAzyme motif to drive another cycle of activation. During the cyclic process, a very small number of target miRNAs can initiate the cleavage of many fluorophore-labeled substrate strands from AuNP surface, providing an amplified fluorescent signal of the target miRNA and, thus, offering high detection sensitivity.


Properties of quantum systems via diagonalization of transition amplitudes. I. Discretization effects.
We analyze the method for calculation of properties of nonrelativistic quantum systems based on exact diagonalization of space-discretized short-time evolution operators. In this paper we present a detailed analysis of the errors associated with space discretization. Approaches using direct diagonalization of real-space discretized Hamiltonians lead to polynomial errors in discretization spacing Delta . Here we show that the method based on the diagonalization of the short-time evolution operators leads to substantially smaller discretization errors, vanishing exponentially with 1/Delta(2). As a result, the presented calculation scheme is particularly well suited for numerical studies of few-body quantum systems. The analytically derived discretization errors estimates are numerically shown to hold for several models. In the follow up paper [I. Vidanović, A. Bogojević, A. Balaz, and A. Belić, Phys. Rev. E 80, 066706 (2009)] we present and analyze substantial improvements that result from the merger of this approach with the recently introduced effective-action scheme for high-precision calculation of short-time propagation.


Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of Ito channel complex.
DPP10 is a transmembrane glycosylated protein belonging to the family of dipeptidyl aminopeptidase-like proteins (DPPLs). DPPLs are auxiliary subunits involved in the regulation of voltage-gated Kv4 channels, key determinants of cardiac and neuronal excitability. Although it is known that DPPLs are needed to generate native-like currents in heterologous expression systems, the molecular basis of this involvement are still poorly defined. In this study, we investigated the functional relevance of DPP10 glycosylation in modulating Kv4.3 channel activities. Using transfected Chinese hamster ovary (CHO) cells to reconstitute Kv4 complex, we show that the pharmacological inhibition of DPP10 glycosylation by tunicamycin and neuraminidase affects transient outward potassium current (I (to)) kinetics. Tunicamycin completely blocked DPP10 glycosylation and reduced DPP10 cell surface expression. The accelerating effects of DPP10 on Kv4.3 current kinetics, i.e. on inactivation and recovery from inactivation, were abolished. Neuraminidase produced different effects on current kinetics than tunicamycin, i.e., shifted the voltage dependence to more negative potentials. The effects of tunicamycin on the native I (to) currents of human atrial myocytes expressing DPP10 were similar to those of the KV4.3/KChIP2/DPP10 complex in CHO cells. Our results suggest that N-linked glycosylation of DPP10 plays an important role in modulating Kv4 channel activities.


Mapping the spatial neighborhood of the regulatory 6S RNA bound to Escherichia coli RNA polymerase holoenzyme.
Bacterial 6S RNA interacts specifically with RNA polymerase acting as transcriptional regulator. Until now, no detailed characterization of the spatial arrangement of the non-coding RNA within the three-dimensional structure of RNA polymerase has been performed. Here we present results obtained with the chemical nuclease FeBABE tethered to distinct positions of RNA polymerase σ(70) subunit. 6S RNA complexes were formed with a collection of RNA polymerases, where the cleavage reagent had been fused to σ(70) single-cysteine variants close to regions involved in promoter recognition. FeBABE-induced cleavage sites within the 6S RNA structure were identified, indicating close spatial neighborhood between σ(70) single-cysteine side chains and defined positions of the 6S RNA structure. Our analysis demonstrates close proximity between the 6S RNA internal hairpin and σ(70) domain 4.2, normally involved in recognition of -35 promoter DNA. Defined sections of the internal 6S RNA stem structure flanking the central bubble are positioned near conserved σ(70) domains 3.1, 2.3 and 2.1, which are implicated in binding and melting DNA promoters between the -10 and -35 elements. Moreover, we show that U44 of 6S RNA is located near RNA polymerase active site (σ(70) domain 3.2), fully consistent with its function as starting nucleotide in RNA-directed pRNA transcription. No neighboring contacts were detected between 6S RNA and σ(70) region 1.2 or between σ(70) and the 6S RNA closing stem structure (residues 1-41 and 144-184). Results were used to dock a structural model of 6S RNA to the known three-dimensional structure of Escherichia coli σ(70) RNA polymerase holoenzyme.


[Congenital dislocation of the hip: an osteo-neural growth disturbance (author's transl)].
Congenital dislocation of the hip may be readily explained as the result of the osteo-neural growth-in-length disproportion. The theoretical concept is supported by experimental findings in frog tadpoles with "congenital" dislocation of the knee joint produced by osteolathyrogenic diet. In cleared specimens with selective staining of the nervous trunks according to Williams (1943) a growth inhibition of the sciatic nerve responsible for the proximal shift (dislocation) of the tibia may be noted. The tibia is adapted to the growth peculiarities of the sciatic nerve in an essentially similar way like the bony neurocranial capsule to the growing brain. The suggested pathogenetic mechanism appears to apply even to the congenital dislocation of the hip in man.


Renal function in patients treated with tobramycin-cefuroxime or tobramycin-penicillin G.
In order to evaluate the potentiating effect of cefuroxime on tobramycin nephrotoxicity 21 immunocompromised patients with suspected septicaemia were randomized to treatment with either tobramycin + cefuroxime or tobramycin + penicillin G. 51Chromium-EDTA clearance, serum creatinine, serum beta 2-microglobulin, urinary, alanine aminopeptidase, urinary N-acetyl-beta-D-glucosaminidase and urinary beta 2-microglobulin were measured during a nine day course of the antibiotic combinations. Enzymuria and a small but significant decrease of 51Chromium-EDTA clearance of equal magnitude in both treatment groups occurred. However the results cannot be extrapolated to other doses and treatment times than used in the study.


Treatment of infrabony periodontal defects using a resorbable biopolymer of hyaluronic acid: a randomized clinical trial.
This randomized clinical study examined the use of hyaluronic acid to treat infrabony periodontal defects over a period of 24 months. Forty subjects with a two-wall infrabony defect (probing depth [PD] >= 7 mm; clinical attachment level [CAL] >= 7 mm) were selected. The defects were randomly divided into two groups: sites treated with hyaluronic acid (test group) and those treated with open flap debridement (control group). The 12- and 24-month evaluations were based on clinical and radiographic parameters. The primary outcome variable was CAL. Test defects shows a mean CAL gain of 1.9 ± 1.8 mm, while the control defects yielded a significantly lower gain of 1.1 ± 0.7 mm. PD reduction was also significantly higher in the test group (1.6 ± 1.2 mm) than in the control group (0.8 ± 0.5 mm). Frequency distribution analysis of the study outcomes indicated that hyaluronic acid increased the predictability of clinically significant results (CAL gains >= 2 mm and PD reduction >= 2 mm) in the test group compared with the controls. The treatment of infrabony defects with hyaluronic acid offered an additional benefit in terms of CAL gain, PD reduction, and predictability compared to treatment with open flap debridement.


Immediate and intermediate-term results of optical coherence tomography guided atherectomy in the treatment of peripheral arterial disease: Initial results from the VISION trial.
Long-term patency rates for percutaneous peripheral arterial interventions are suboptimal. Optical coherence tomography (OCT) guided atherectomy may yield superior patency by optimizing plaque removal while preserving the tunica media and adventitia. The VISION study is a multicenter prospective study of patients with peripheral arterial disease undergoing OCT guided atherectomy with the Pantheris™ device. In 11 patients enrolled in a single center, we report procedural and clinical outcomes, at 30days and 6months. The mean age was 63±11years and 73% (n=8) were men. The target lesion was in the superficial femoral artery in 82% (n=9) of the patients. Mean stenosis severity was 87%±10% and mean lesion length was 39±31mm. Procedural success was observed in all patients with no device related complications. Mean post-atherectomy stenosis was 18%±15%. Almost all excised tissue consisted of intimal plaque (94%). At 30days, significant improvements in Rutherford class, VascuQoL scores and ABI were observed, 0.9±0.8 vs. 3.1±0.7 (p=0.01), 4.9±1.9 vs. 3.6±1.5 (p=0.03) and 1.04±0.19 vs. 0.80±0.19 (p<0.01) respectively. At 6months, there were significant improvements in Rutherford class (1.0±1.0 vs. 3.1±0.7, p=0.01) and ABI (0.93±0.19 versus 0.80±0.19, p=0.02) but not in VascuQoL scores (3.7±1.4 versus 3.6±1.5, p=0.48). Target lesion revascularization occurred in 18% (n=2) of the patients. OCT guided atherectomy resulted in high procedural success, no device related complications and encouraging results up to 6months. Histological analysis suggested little injury to the media and adventitia. Larger studies are needed to confirm the efficacy of this approach.


[Genetic characterization and correlation among fragments of HN gene of the field Newcastle disease viruses].
Twenty-four isolates of Newcastle disease virus (NDV) prevailing during 1997 -- 2005 in China were collected. These isolates were purified by CEF plaque assay and replicated in SPF chicken embryos. The hemagglutinin-neuraminidase (HN) genes of these viruses were cloned and sequenced. The HN gene sequences of thirty-six NDV reference strains in GenBank were also used in this study. The amino acid homologing of these viruses were compared and analyzed. The correlations among different fragments of HN gene were also analyzed. The results indicated that the homology of Chinese field NDV strains was 94.4%-99.4%, but 86.9%-89% compared with LaSota and Clone30, 87.9%-89.9% to F48E9, and 87.2%-96.2% to foreign NDV strains. There had the nearest distances among Chinese NDV isolates as compared with that of the LaSota, Clone30 and F48E9 by the phylogenetic tree. However, the distances of seven foreign NDV isolates were very close to Chinese NDV isolates as compared with these of the other foreign NDV isolates. We also found that all the Chinese field isolates were devoid of glycosylation site in position 538 -- 540. There were good correlations between different length amino acid fragments and the genomes of HN, especially the 5'-terminus first 80aa.


The National Association of Medical Examiners Position Paper: Second Autopsies.
Second autopsies are uncommon in the United States yet are of significant public value. A second autopsy may be sought when the first autopsy findings are disputed, considered biased, or inadequately communicated. Second autopsies are technically and interpretatively difficult and usually rely heavily on investigative information, first autopsy findings, and additional documentation from the first autopsy. Medicolegal second autopsies should be performed only by experienced, board-certified forensic pathologists. Pathologists performing second autopsies should acknowledge and disclose the limitations of second autopsies. The first autopsy pathologist should recognize the quality assurance value of a second autopsy and fully disclose autopsy documentation to the second autopsy pathologist, if permitted by jurisdictional law.


Local hormone therapy for genitourinary syndrome of menopause in breast cancer patients: is it safe?
The genitourinary syndrome of menopause (GSM) is a frequent complaint among breast cancer (BC) survivors that lead to an important affection of their quality of life (QoL). Lifestyle measures such as smoking cessation or regular sexual activity are usually insufficient to significantly improve GMS and although therapies such as lubricants and polycarbophil moisturized gels are considered first-line therapies to alleviate symptoms of vulvovaginal atrophy, these non-hormonal options are not able to reverse atrophy once it occurs. Instead, this complaint is corrected by local estrogens. The estrogen vaginal treatment usually used to treat GSM, is an issue of concern in this group due to the possible negative effect over the BC outcomes. On the other hand, the worsening of QoL in these patients due to symptoms related to GSM can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly. The goal of this review is to contribute to health care professionals to make an informed decision to care for their BC patients.


Synthesis, material properties, and biocompatibility of a novel self-cross-linkable poly(caprolactone fumarate) as an injectable tissue engineering scaffold.
A novel self-cross-linkable and biodegradable macromer, poly(caprolactone fumarate) (PCLF), has been developed for guided bone regeneration. This macromer is a copolymer of fumaryl chloride, which contains double bonds for in-situ cross-linking, and poly(epsilon-caprolactone), which has a flexible chain to facilitate self-cross-linkability. PCLF was characterized with Fourier transform infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and gel permeation chromatography. Porous scaffolds were fabricated with sodium chloride particles as the porogen and a chemical initiation system. The PCLF scaffolds were characterized with scanning electron microscopy and micro-computed-tomography. The cytotoxicity and in vivo biocompatibility of PCLF were also assessed. Our results suggest that this novel copolymer, PCLF, is an injectable, self-cross-linkable, and biocompatible macromer that may be potentially used as a scaffold for tissue engineering applications.


Moderate to severe hemolytic disease of the newborn in a referral centre in Saudi Arabia.
All infants undergoing an exchange transfusion at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, during a 7½-year period, were studied retrospectively. One hundred thirteen exchange transfusions were performed in 57 infants. Of 45 infants with hemolytic disease, three were still newborn, The 42 liveborn infants required 93 exchange transfusion for hemolytic disease of the newborn. In 15 infants requiring 20 exchange transfusions, the indication was hyperbilirubinemia of prematurity. Rh-hemolytic disease of the newborn was the most common etiology of severe anemia or hypebilirubinemia requiring an exchange transfusion. Isoimmunization was due to anti-D in 34 patients, anti-c in three, and anti-E and anti-C in one, anti-A and anti-B in four and anti-Jk(b) in one patient. One of these cases of hemolytic disease of the newborn was due to G6PD deficiency, and in one case the cause was unknown, The incidence of moderate to severe Rh-hemolytic disease of the newborn was 7.0/1000 births contributing significantly to perinatal mortality (6.3%) and to early neonatal mortality (7.0%) in the hospital. Rh-hemolytic disease of the newborn is a problem in Saudi Arabia that could be reduced with improved antenatal and obstetric care and ante- and postnatal anti-D-globulin prophylaxis.


Novel spatial filter for SSVEP-based BCI: A generated reference filter approach.
Steady state visual evoked potential (SSVEP)-based brain computer interface (BCI) systems can be realised using only one electrode; however, due to the inter-user and inter-trial differences, the handling of multiple electrode is preferred. This raises the problem of evaluating information from multiple electrode signals. To solve this problem, we developed a novel spatial filtering method (Generated Reference Filter) for SSVEP-based BCIs. In our method an artificial reference signal is generated by a combination of reference electrode signals. Multiple regression analysis (MRA) was used to determine the optimal weight coefficients for signal combination. The filtered signal was obtained by subtraction. The method was tested on a SSVEP dataset and compared with minimum energy combination and common reference methods, namely the surface Laplacian technique and common average referencing. The newly developed method provided more effective filtering and therefore higher SSVEP detection accuracy was obtained. It was also more robust against subject-to-subject and trial-to-trial variability as the artificial reference signal was recalculated for each detection round. No special preparation is required, and the method is easy to implement. These experimental results indicate that the proposed method can be used confidently with SSVEP-based BCI systems.


Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia.
The existence of T cells capable of inhibiting in vitro hematopoiesis has been shown in aplastic anemia (AA), although whether such inhibition is mediated by a specific immune reaction involving an HLA allele remained unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched with CD34+ cells that had been cultured for one week in the presence of colony-stimulating factors as well as allogeneic CD34+ cells of a normal individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells may contribute to the pathogenesis of AA.


Intra-amygdala muscimol injections impair freezing and place avoidance in aversive contextual conditioning.
Rats were trained by shocking them in a closed compartment. When subsequently tested in the same closed compartment with no shock, normal rats showed an increased tendency to freeze. They also showed an increased tendency to actively avoid the compartment when given access to an adjacent neutral compartment for the first time. Amygdala inactivation with bilateral muscimol injections before training attenuated freezing and eliminated avoidance during the test. Rats trained in a normal state and given intra-amygdala muscimol injections before the test did not freeze or avoid the shock-paired compartment. This pattern of effects suggests that amygdala inactivation during training impaired acquisition of a conditioned response (CR) due either to inactivation of a neural substrate essential for its storage or to elimination of a memory modulation effect that facilitates its storage in some other brain region(s). The elimination of both freezing and active avoidance by amygdala inactivation during testing suggests that neither of these behaviors is the CR. The possibility that the CR is a set of internal responses that produces both freezing and avoidance as well as other behavioral effects is discussed.


Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses.
Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably.IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world's virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.


Effects of sewage sludge hydrochar on emissions of the climate-relevant trace gases N2O and CO2 from loamy sand soil.
This work explores the effects of amending a loamy sand soil with hydrochars having different physicochemcial characteristics. The effects of different hydrochars on emissions of the greenhouse gases nitrous oxide (N2O) and carbon dioxide (CO2) were investigated together with the relationship between the hydrochar's mineral nitrogen content and the soil microbial biomass. Soil samples were amended with eleven different hydrochars and feedstocks having different carbon and nitrogen contents at application rates of 5 t ha-1 and 25 t ha-1. Microbial immobilization was the main mineral nitrogen sink in soil following hydrochar application. Moreover, the processing conditions applied during hydrochar production (i.e., the pyrolysis temperature and residence time) had significant effects on N2O and CO2 emissions: treatment with incubated hydrochars yielded significantly lower N2O emissions than treatment with non-carbonized feedstocks, particularly at the highest level of hydrochar application (25 t ha-1). Further analysis revealed that increasing the process temperature and residence time during hdyrochar production significantly increased the final product's total organic carbon content but reduced its content of hot water extractable carbon. Hydrochars produced with higher process temperatures and longer residence times therefore yielded lower CO2 emissions during a 44-day incubation experiment than raw feedstocks or hydrochars produced under less severe conditions. Hydrochars formed from sewage sludge at high process temperatures and with long residence times are thus promising soil additives for reducing GHG emissions.


LRBA signalosomes activate vasopressin-induced AQP2 trafficking at recycling endosomes.
Aquaporin-2 (AQP2) water channels are proteins that are recycled between intracellular vesicles and the apical plasma membrane in renal collecting ducts. Lipopolysaccharide-responsive beige-like anchor protein (LRBA) is a protein kinase A (PKA) anchoring protein that creates compartmentalized PKA signalling responsible for AQP2 phosphorylation. In response to increased plasma osmolality, vasopressin/cyclic adenosine monophosphate (cAMP)/PKA signalling phosphorylates AQP2, promoting AQP2 trafficking into the apical plasma membrane and increasing water reabsorption from urine. However, the molecular mechanisms by which LRBA mediates vasopressin-induced AQP2 phosphorylation remain unknown. To investigate AQP2 intracellular localization and phosphorylation status in vivo, a density gradient ultracentrifugation technique was combined with an in situ proximity ligation assay, super-resolution structured illumination microscopy and immunoelectron microscopy. Most of the AQP2 was localized on the recycling endosome in the presence of tolvaptan, a vasopressin type 2 receptor (V2R) antagonist. Desmopressin, a V2R agonist, phosphorylated AQP2, translocating it from the recycling endosome to the apical plasma membrane. In contrast, LRBA was constitutively localized at the recycling endosome. Therefore, LRBA and AQP2 were well colocalized in the absence of vasopressin stimulation. The loss of LRBA/PKA signalling by Lrba knockout impaired vasopressin-induced AQP2 phosphorylation, resulting in AQP2 retention at the recycling endosome. Defective AQP2 trafficking caused low urinary concentrating ability in Lrba-/- mice. The LRBA-PKA complex created compartmentalized PKA signalling at the recycling endosome, which facilitated AQP2 phosphorylation in response to vasopressin. KEY POINTS: Membrane proteins are continuously internalized into the endosomal system via endocytosis, after which they are either recycled back to the plasma membrane or degraded at the lysosome. In T cells, lipopolysaccharide-responsive beige-like anchor protein (LRBA) binds directly to the cytotoxic T lymphocyte antigen 4 (CTLA-4), a checkpoint immune molecule, to prevent CTLA-4 lysosomal degradation and promote its vesicle recycling. LRBA has different physiological functions in renal collecting ducts. LRBA and aquaporin-2 (AQP2) water channels were colocalized on the recycling endosome in vivo in the absence of the anti-diuretic hormone vasopressin. LRBA promoted vasopressin-induced AQP2 trafficking, increasing water reabsorption from urine via AQP2. LRBA determined renal responsiveness to vasopressin at recycling endosomes. LRBA is a ubiquitously expressed anchor protein. LRBA signalosomes might regulate membrane trafficking of several constitutively recycled proteins at recycling endosomes.


Divide-and-conquer multiple alignment with segment-based constraints.
A large number of methods for multiple sequence alignment are currently available. Recent benchmarking tests demonstrated that strengths and drawbacks of these methods differ substantially. Global strategies can be outperformed by approaches based on local similarities and vice versa, depending on the characteristics of the input sequences. In recent years, mixed approaches that include both global and local features have shown promising results. Herein, we introduce a new algorithm for multiple sequence alignment that integrates the global divide-and-conquer approach with the local segment-based approach, thereby combining the strengths of those two strategies.


Rhythmic expression of DEC2 protein in vitro and in vivo.
Basic helix-loop-helix (bHLH) transcription factor DEC2 (bHLHE41/Sharp1) is one of the clock genes that show a circadian rhythm in various tissues. DEC2 regulates differentiation, sleep length, tumor cell invasion and apoptosis. Although studies have been conducted on the rhythmic expression of DEC2 mRNA in various tissues, the precise molecular mechanism of DEC2 expression is poorly understood. In the present study, we examined whether DEC2 protein had a rhythmic expression. Western blot analysis for DEC2 protein revealed a rhythmic expression in mouse liver, lung and muscle and in MCF-7 and U2OS cells. In addition, AMP-activated protein kinase (AMPK) activity (phosphorylation of AMPK) in mouse embryonic fibroblasts (MEFs) exhibited a rhythmic expression under the condition of medium change or glucose-depleted medium. However, the rhythmic expression of DEC2 in MEF gradually decreased in time under these conditions. The medium change affected the levels of DEC2 protein and phosphorylation of AMPK. In addition, the levels of DEC2 protein showed a rhythmic expression in vivo and in MCF-7 and U2OS cells. The results showed that the phosphorylation of AMPK immunoreactivity was strongly detected in the liver and lung of DEC2 knockout mice compared with that of wild-type mice. These results may provide new insights into rhythmic expression and the regulation between DEC2 protein and AMPK activity.


Predicting behavioral and brain markers of inhibitory control at preschool age from early measures of executive attention.
Inhibitory control (IC) is the ability to prevent prepotent responses when inappropriate. Longitudinal research on IC development has mainly focused on early childhood and adolescence, while research on IC development in the first years of life is still scarce. To address this gap in the literature, we explored the association between executive attention (EA) and elementary forms of IC in infancy and toddlerhood, with individual differences in IC later at 5 years of age. We conducted a five-wave longitudinal study in which children's EA and IC (n = 96) were tested at the age of 9 and 16 months and 2, 3, and 5 years. Children performed various age-appropriate EA and IC tasks in each wave, measuring inhibition of attention, endogenous control of attention, inhibition of the response, and conflict inhibition. At 5 years of age, IC was measured with a Go/No-go task while recording event-related potentials. After correlation analyses, structural equation model analyses were performed to predict IC at 5 years of age from EA and early IC measures. The results revealed that EA at 9 months predicted IC measures at 2 years of age. Likewise, measures of IC at 2 years predicted performance on the Go/No-go task at behavioral and neural levels. No direct association was found between EA at 9 months and IC at 5 years of age. We further observed that some EA and IC measures were not associated across time. As we expected, EA skills in infancy and toddlerhood were related to better performance of children on IC tasks, toghether with a more mature inhibition-related brain functioning. Altogether, the results indicate that IC in early childhood could be predicted from EA and IC at 9 months and 2 years of age and suggest that the early emergence of IC relies on the development of particular EA and basic IC skills. However, some discontinuities in the longitudinal development of IC are observed in the first 5 years of life. These findings provide further support for the hierarchical model of IC development.


The association of metabolic syndrome and aging with cognition in Asian men.
The present cross-sectional study examined the associations of individual metabolic factors and age with the short-term memory and perceptual capacity in 472 healthy Asian men. The symbol digit and digit span tests from the Swedish Performance Evaluation System were used to assess the perceptual capacity and memory cognitive domains. Linear regression with the stepwise method, and multivariate analyses of the General Linear Model with the Bonferroni correction for multiple comparisons were carried out with the SPSS 21.0 package. High blood pressure and HDL were not significantly associated with either short-term memory or perceptual capacity. Age and glucose level were negatively associated but regular physical exercise was positively associated with perceptual capacity. On the other hand, high triglyceride level (TG) was positively associated but high waist/height ratio was negatively associated with short-term memory. When men without any component of the metabolic syndrome (MetS) were compared with men with one, two or three or more components of MetS, no significant differences in cognitive performance were noted. Not all the metabolic factors were significantly associated with short-term memory or the perceptual capacity domains. Those that were did not show a sufficiently consistent pattern of association to support a role for MetS as a whole in cognitive decline with aging. It may not be meaningful to evaluate the association of MetS as a whole with cognition.


[Ultrastructure of cells of rat lymphatic organs during continuous irradiation].
Changes in the ultrastructures of lymphatic organs of rats observed from the 2nd to 22nd day following continuous irradiation with gamma rays at a daily dose of 115 mGy (exposition: 12 R/day) are described. The maximum of destructive changes in lymphocytes was observed on the 11th to the 14th day of irradiation. A gradual balance between dystrophic and regenerative processes was achieved on the 18th day. In this connection to correlation could be determined between the ultrastructural changes described and the fluctuations of lymphocyte numbers in the lymphatic organs and peripheral blood during continuous irradiation.


Lack of effect of cecectomy on oxygen consumption and colonic temperature of germfree rats.
Oxygen consumption and colonic temperature of germfree rats are lower than those of conventional and conventionalized rats. Cecectomy of weanling germfree rats prevents the development of the very large ceca characteristic of ordinary germfree rats but did not increase oxygen consumption or change colonic temperature.


A new variant of von Willebrand's disease (type I Padua): doublet-organized plasma von Willebrand factor oligomers in the presence of all size multimers.
Type I von Willebrand's disease (vWd) is characterized by a concomitant decrease in plasma of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin cofactor activity (vWf:RCoF), associated with the presence of all-size multimers. As a rule, there is no evidence of intrinsic abnormality in vWf. We describe a family with type I vWd with an abnormal plasma vWf multimer pattern. Analysis of plasma vWf multimeric structure by short-SDS-agarose gel electrophoresis showed an abnormal banding pattern for each vWf oligomer, which was organized as a doublet instead of the normal triplet. The electrophoretic mobility of each component appeared to be normal. Multimeric analysis on a long gel showed all the bands that were detectable in normal subjects, but unlike normals the fast moving satellite stained as the major component. The platelet vWf multimer pattern was normal. The infusion of DDAVP normalized vWf:Ag, vWf:RCoF and VIII:C, but not the abnormal multimer pattern observed on both short- and long-gel electrophoresis. The return of factor VIII/vWf complex to the baseline condition was more rapid than that observed in normal subjects or classic type I vWd patients. Analysis of the subunit fragments in the patients' plasma vWf demonstrated a relatively greater proportion, compared to the normal counterpart, of a 115(140)-kD fragment, which derives from the aminoterminal region of the mature molecule; in contrast, no intact subunit was detectable. These findings indicate a new, previously unreported, variant of type I vWd, which is characterized by plasma vWf oligomers organized as doublets, instead of triplets. The reduced post-DDAVP half-life, and the abnormal subunit fragments of vWf, suggest a molecule characterized by an increased susceptibility to proteolytic degradation. As a result, the decrease in circulating vWf levels may be due to an instability of the abnormal vWf, rather than, or in addition to, a decrease in its synthesis.


Electron microscopic observations on the large subunit of the rat liver ribosome.
Active large subunits obtained by urea treatment of rat liver ribosomes, 59S, were compared with large subunits in intact ribosomes and with the 50S subunits obtained by EDTA treatment. For electron microscopy the specimens were negatively stained or shadow cast. The negatively stained 59S subunits had a slightly ovoidal form; their average dimensions, 244 +/- 17 x 207 +/- 18 A, were very close to the dimensions of the large subunits in intact ribosomes, and lay between the theoretical dimensions for anhydrous and fully hydrated particles that were calculated from the physical properties of the subunits in solution. The shadow-cast preparations showed particles of similar shape. The 50S subunits, which had lost their 5S RNA, were shadow cast at the same time. They appeared to be more spread out than the 59S subunits and had threadlike extensions. In the positively stained regions of uranyl oxalate-stained preparations the 50S particles varied greatly in shape and size, with average dimensions of 330 +/- 21 x 276 +/- 33 A, and showed threadlike extensions like those of the shadow-cast particles. For 50S particles in solution the frictional drag of these extensions probably accounts for their low sedimentation coefficient.


Two applications of transmucosal milled ceramic in implantology: preliminary clinical examples.
Two new implant systems, the Compound Implant and the TFM coping/abutment, are based on the association of titanium in the infrabony portion and a dense milled ceramic in the transgingival portion. The coating of zirconium ceramic on the transmucosal collar of the Compound Implant is particularly indicated for a single-stage surgical implant technique. The isolating properties and the high wettability of this material favor gingival healing and reduce the accumulation of plaque; the esthetic collar permits a supragingival or juxtagingival cervical margin favoring plaque control and minimizing the consequences of tissue remodeling. The hardness of the ceramic also allows it to undergo conventional prophylaxis with ultrasonic scalers without alteration of its surface quality. In addition to the above-mentioned advantages, the TFM coping/abutment, an implant-prosthesis connector in alumina ceramic, for use in a two-stage technique, provides electrogalvanic isolation of the implant, and personalized abutment preparation allows for simplified fabrication of an implant-supported prosthesis.


Graphite oxide flame-retardant polymer nanocomposites.
Graphite oxide (GO) polymer nanocomposites were developed at 1, 5, and 10 wt % GO with polycarbonate (PC), acrylonitrile butadiene styrene, and high-impact polystyrene for the purpose of evaluating the flammability reduction and material properties of the resulting systems. The overall morphology and dispersion of GO within the polymer nanocomposites were studied by scanning electron microscopy and optical microscopy; GO was found to be well-dispersed throughout the matrix without the formation of large aggregates. Mechanical testing was performed using dynamic mechanical analysis to measure the storage modulus, which increased for all polymer systems with increased GO loading. Microscale oxygen consumption calorimetry revealed that the addition of GO reduced the total heat release and peak heat release rates in all systems, and GO-PC composites demonstrated very fast self-extinguishing times in vertical open flame tests, which are important to some regulatory fire safety applications.


MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses.
Multivalent molecules with repetitive structures including bacterial capsular polysaccharides and viral capsids elicit antibody responses through B cell receptor (BCR) crosslinking in the absence of T cell help. We report that immunization with these T cell-independent type 2 (TI-2) antigens causes up-regulation of endogenous retrovirus (ERV) RNAs in antigen-specific mouse B cells. These RNAs are detected via a mitochondrial antiviral signaling protein (MAVS)-dependent RNA sensing pathway or reverse-transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave of signaling that promotes specific immunoglobulin M production. Deficiency of both MAVS and cGAS, or treatment of MAVS-deficient mice with reverse transcriptase inhibitors, dramatically inhibits TI-2 antibody responses. These findings suggest that ERV and two innate sensing pathways that detect them are integral components of the TI-2 B cell signaling apparatus.


Oxygen-sensing pathways and the pulmonary circulation.
The unique property of the pulmonary circulation to constrict in response to hypoxia, rather than dilate, brings advantages in both health and disease. Hypoxic pulmonary vasoconstriction (HPV) acts to optimise ventilation-perfusion matching - this is important clinically both in focal disease (such as pneumonia) and in one-lung ventilation during anaesthesia for thoracic surgery. However, during global hypoxia such as that encountered at high altitude, generalised pulmonary vasoconstriction can lead to pulmonary hypertension. There is now a growing body of evidence that links the hypoxia-inducible factor (HIF) pathway and pulmonary vascular tone - in both acute and chronic settings. Genetic and pharmacological alterations to all key components of this pathway (VHL - von Hippel-Lindau ubiquitin E3 ligase; PHD2 - prolyl hydroxylase domain protein 2; HIF1 and HIF2) have clear effects on the pulmonary circulation, particularly in hypoxia. Furthermore, knowledge of the molecular biology of the prolyl hydroxylase enzymes has led to an extensive and ongoing body of research into the importance of iron in both HPV and pulmonary hypertension. This review will explore these relationships in more detail and discuss future avenues of research.


The effect of paclitaxel-eluting covered metal stents versus covered metal stents in a rabbit esophageal squamous carcinoma model.
The use of self-expanding metallic stents (SEMSs) is the current treatment of choice for malignant gastrointestinal obstructions. However, these stents can promote only drainage and have no antitumor effect. Some studies have reported that drug-eluting SEMSs may have tumor inhibition potential. The aim of this study was to evaluate the efficiency and safety of paclitaxel-eluting SEMSs (PEMSs) in rabbit esophageal cancer models. A PEMS was covered with a paclitaxel-incorporated membrane, in which the concentration of paclitaxel was 10% (wt/vol). The rabbit models were created endoscopically. Then, a PEMS or SEMS was endoscopically inserted into the rabbit esophagus. Two weeks after stent placement, the rabbits were sacrificed, and we evaluated the tumor volume, area of the wall defect, area of the tumor under endoscopic ultrasound (EUS) before and after stent placement, status of the proximal esophageal obstruction, tumor metastasis food-intake and weight loss. A total of 26 rabbits received stent insertion and survived until sacrifice, and migration occurred in 4 cases, 3 in SEMS group and 1 in PEMS group. For the remaining 22 rabbits, at the sacrificed time, the average tumor volume was 7.00±4.30 cm3 in the SEMS group and 0.94±1.51 cm3 in the PEMS group (P<0.05). The area of the esophageal wall defect was 0.70±0.63 cm2 in the SEMS group and 0.17±0.16 cm2 in the PEMS group (P<0.05). The tumor area under EUS was 4.40±1.47 cm2 in the SEMS group and 1.30±1.06 cm2 in the PEMS group (P<0.05). At the time of stent placement, tumor area under EUS was comparable in the two groups. Other indices did not significantly differ between the two groups. SEMS and PEMS are both safe and effective to relieve dysphagia in rabbit esophageal cancer models. A PEMS can serve as an alternative tool for advanced esophageal cancer that may inhibit tumor growth by serving as a drug sustained-release platform. Clinical trials of the stent are warranted in the future.


Enhancing Two-Electron Reaction Contribution in MnO2 Cathode Material by Structural Engineering for Stable Cycling in Aqueous Zn Batteries.
MnO2 is a promising cathode for aqueous Zn batteries. However, the cycling stability is seriously hindered by active material dissolution, and the pre-addition of Mn2+ salts in electrolytes is widely required. Herein, we propose a structural engineering strategy for MnO2 to enhance the capacity contribution from the reversible two-electron transfer reaction of MnO2/Mn2+ and realize stable cycling in Mn2+-free electrolytes. By compositing with MoO3, MnO2 exhibits weakened Mn-O bonds, more oxygen vacancies, spontaneous generation of structural water, and thus a lowered energy barrier for Mn release during discharge. Meanwhile, the composite material presents stronger electrostatic attractions for dissolved Mn2+, which ensures highly reversible re-deposition during charge. As a result, the mass ratios between materials undergoing reversible two-electron and one-electron transfer reactions increase from 0.85 in MnO2 to 1.68 in the MnO2/MoO3 composite material. In the ZnSO4 electrolyte, the MnO2/MoO3 cathode achieves 92.6% capacity retention after 300 cycles at 0.1 A g-1 (>1900 h), superior to 62.7% for MnO2. MnO2/MoO3 also retains 80.1% capacity after 16 000 cycles at 1 A g-1 (>3200 h). This work presents an effective path to realize stable cycling of MnO2 in Zn batteries.


Comparative neuroimaging of sex differences in human and mouse brain anatomy.
In vivo neuroimaging studies have established several reproducible volumetric sex differences in the human brain, but the causes of such differences are hard to parse. While mouse models are useful for understanding the cellular and mechanistic bases of sex-biased brain development in mammals, there have been no attempts to formally compare mouse and human sex differences across the whole brain to ascertain how well they translate. Addressing this question would shed critical light on use of the mouse as a translational model for sex differences in the human brain and provide insights into the degree to which sex differences in brain volume are conserved across mammals. Here, we use cross-species structural magnetic resonance imaging to carry out the first comparative neuroimaging study of sex-biased neuroanatomical organization of the human and mouse brain. In line with previous findings, we observe that in humans, males have significantly larger and more variable total brain volume; these sex differences are not mirrored in mice. After controlling for total brain volume, we observe modest cross-species congruence in the volumetric effect size of sex across 60 homologous brain regions (r=0.30; e.g.: M>F amygdala, hippocampus, bed nucleus of the stria terminalis, and hypothalamus and F>M anterior cingulate, somatosensory, and primary auditory cortices). This cross-species congruence is greater in the cortex (r=0.33) than non-cortex (r=0.16). By incorporating regional measures of gene expression in both species, we reveal that cortical regions with greater cross-species congruence in volumetric sex differences also show greater cross-species congruence in the expression profile of 2835 homologous genes. This phenomenon differentiates primary sensory regions with high congruence of sex effects and gene expression from limbic cortices where congruence in both these features was weaker between species. These findings help identify aspects of sex-biased brain anatomy present in mice that are retained, lost, or inverted in humans. More broadly, our work provides an empirical basis for targeting mechanistic studies of sex-biased brain development in mice to brain regions that best echo sex-biased brain development in humans.


Computers getting the drift.
Natural language processing is the study of computer programs that can understand and produce human language. An important goal in the research to produce such technology is identifying the right meaning of words and phrases. In this paper, we give an overview of current research in three areas: (i) inducing word meaning; (ii) distinguishing different meanings of words used in context; and (iii) determining when the meaning of a phrase cannot straightforwardly be obtained from its parts. Manual construction of resources is labour intensive and costly and furthermore may not reflect the meanings that are useful for the task or data at hand. For this reason, we focus particularly on systems that use samples of language data to learn about meanings, rather than examples annotated by humans.


Intracoronary versus intravenous adenosine to assess fractional flow reserve: a systematic review and meta-analysis.
Intravenous infusion of adenosine is the reference method to measure fractional flow reserve (FFR). Intracoronary boluses are often used because of time and convenience, but their effectiveness has yet to be assessed. We conducted a systematic review and meta-analysis of prospective studies directly comparing intravenous and intracoronary adenosine administration for FFR measurement. FFR values and prevalence of functionally critical lesions obtained with the different methods of adenosine administration were compared. Twelve studies evaluating 781 lesions from 731 patients were included (63.7 years, 25.5% women, median FFR 0.82). FFR values were significantly lower with intravenous adenosine than with intracoronary adenosine [mean difference 0.01, 95% confidence interval (CI) 0.00-0.02, P = 0.005], even if no significant differences were observed when only high doses of intracoronary adenosine (≥150 μg) were considered. The prevalence of functionally critical lesions did not significantly differ between intracoronary and intravenous adenosine. Concerning the use of different doses of intracoronary adenosine, low doses (≤60 μg) were associated with higher FFR values (mean difference 0.02, 95% CI 0.01-0.03, P < 0.001) and fewer functionally critical lesions (OR 0.57, 95% CI 0.40-0.81, P = 0.002) compared with high doses. Meta-regression analysis did not show any significant interaction between the way of adenosine administration and main clinical features. Intracoronary adenosine was associated with a higher incidence of atrioventricular blocks, whereas angina and/or systemic symptoms were more frequent with intravenous adenosine. Intracoronary adenosine might be as effective as intravenous adenosine to measure FFR, provided that adequate doses are used. Intracoronary adenosine represents a valuable alternative to intravenous adenosine whenever appropriately administered.


Using sponsorship to promote health messages to children.
A survey of children aged 8 to 14 years attending a three-day football clinic was undertaken to examine the relative impact of different sponsorship strategies used to promote health messages. It was found that promotional clothing worn by role models was an effective method for promoting a specific health message (i.e., "Smoking? No Way!"). Personal endorsement of the health message by an external role model and, to a lesser extent, personal endorsement by clinic leaders and promotional clothing worn by clinic leaders and external role models were also effective in promoting a general health message (i.e., "Don't smoke"). The implications for health sponsorship and the promotion of commercial products to children are discussed.


Preparing for the Next Pandemic: Has COVID-19 Changed American Attitudes?
Coronavirus disease 2019 (COVID-19) and future pandemics have become a reality, and planners must understand how attitudes during COVID-19 may influence future preparedness activities. This study explores how personal experiences of Americans during the pandemic, attitudes about institutions, and views of social change could either pose challenges or help with planning for the next pandemic. A longitudinal survey capturing health attitudes and COVD-19-related experiences was fielded 3 times over the course of the pandemic among historically underserved individuals in US society (racial/ethnic minority and low-income populations). COVID-19-related experiences increased over time. Attitudes about federal and state government and businesses' ability to respond to the pandemic varied by COVID-19-related experience and having any COVID-19-related experience was associated with a lower likelihood of reporting positive attitudes about institutions. Respondents generally perceived that COVID-19 presented an opportunity for positive social change, and those with COVID-19-related experiences had the greatest likelihood of selecting "reduce income inequality" as their top prioritized change. Those with COVID-19-related experiences were less likely to endorse other policy priorities such as protecting freedoms. Anticipating potential backlash or other sentiments could improve pandemic responsiveness. Strengthening public institutions is crucial to ensuring their effectiveness during a pandemic. Pandemic planning could exploit opportunities to take other social policy actions where views seem to converge.


Nephrotoxicity in cancer treatment: An overview.
Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment. The kidney is an important elimination pathway for many antineoplastic drugs and their metabolites, which occurs by glomerular filtration and tubular secretion. Chemotherapeutic agents, both conventional cytotoxic agents and molecularly targeted agents, can affect any segment of the nephron including its microvasculature, leading to many clinical manifestations such as proteinuria, hypertension, electrolyte disturbances, glomerulopathy, acute and chronic interstitial nephritis, acute kidney injury and at times chronic kidney disease. The clinician should be alert to recognize several factors that may maximize renal dysfunction and contribute to the increased incidence of nephrotoxicity associated with these drugs, such as intravascular volume depletion, the associated use of nonchemotherapeutic nephrotoxic drugs (analgesics, antibiotics, proton pump inhibitors, and bone-targeted therapies), radiographic ionic contrast media or radiation therapy, urinary tract obstruction, and intrinsic renal disease. Identification of patients at higher risk for nephrotoxicity may allow the prevention or at least reduction in the development and severity of this adverse effect. Therefore, the aim of this brief review is to provide currently available evidences on oncologic drug-related nephrotoxicity.


Effect of enoxacin, norfloxacin and pefloxacin on polymorphonuclear leukocytes chemiluminescence.
We studied the interactions between the neutrophilic granulocytes and three quinolone antibiotics, enoxacin, norfloxacin and pefloxacin, using the luminol-enhanced chemiluminescence method to evaluate the respiratory burst of the cells. Neutrophils obtained from healthy human volunteers were exposed to different therapeutic concentrations of the drugs for one and three hours and then opzonized zymosan was added to stimulate chemiluminescence reaction. None of the three drugs tested exercised any influence on neutrophil function.


Neighbouring group processes in the deamination of protonated phenylalanine derivatives.
The gas-phase fragmentation of protonated phenylalanine and a series of its derivatives (tyrosine, 4-methylphenylalanine, 4-aminophenylalanine, 4-methoxyphenylalanine, 4-tert-butylphenylalanine, 4-fluorophenylalanine, 4-chlorophenylalanine, 4-bromophenylalanine, 4-iodophenylalanine, 4-cyanophenylalanine, 4-nitrophenylalanine, 3-fluorophenylalanine, and 3,4-dichlorophenylalanine) were examined using a combination of low energy CID in a quadrupole ion trap mass spectrometer as well as DFT calculations and RRKM modelling. In particular, the relationship between the electron-donating ability of the substituent and the competitive losses of H2O + CO and NH3 were explored through the application of the Hammett equation. It was found that electron-donating substituents promote the loss of NH3, while electron-withdrawing substituents suppress the loss of NH3 and favour the H2O + CO loss fragmentation channel instead. These observations are consistent with a neighbouring group pathway operating for the loss of NH3. Molecular orbital calculation (at the B3LYP/6-31+G(d,p) level of theory) were also performed for a range of derivatives to compare the relative transition state energy barriers for three competing mechanisms: (i) the combined loss of H2O + CO, which is triggered by an initial intramolecular proton transfer from the ammonium group to hydroxyl OH, followed by the combined loss of H2O and CO to form an immonium ion; (ii) loss of NH3 via an aryl assisted neighbouring group pathway to yield a phenonium ion; (iii) loss of NH3 via a 1,2-hydride migration process, which results in the formation of a benzyl cation. The relative energy barriers for H2O + CO loss remain nearly constant, while that for both NH3 pathways increase as the substituent moves from electron-donating to electron-withdrawing. The relative transition state energy for loss of NH3 via the aryl assisted neighbouring group pathway is always lower than that of the 1,2-hydride migration process. RRKM modelling of the DFT predicted barrier heights suggest that the rate constants for H2O + CO loss are insensitive to the substituent on the ring, while the NH3 loss channels are greatly affected by the substituent. These theoretical results are consistent with the experimental observation of the relative yields of the competing fragmentation channels. Finally, comparisons with published gas phase and condensed phase studies on related systems are made.


Chromosome changes of in situ carcinomas in the female breast.
Eight lesions of ductal carcinoma in situ (DCIS) and one case of benign radial scar were investigated cytogenetically and compared with invasive ductal carcinomas. DCIS was shown to be associated with chromosome changes different from those of invasive carcinomas as concern ploidy levels. All cases exclusively contained abnormal metaphases, also the specimen that was classified as a benign radial scar. No consistent chromosome changes were found. Chromosome no. 1 was most frequently involved in marker chromosome formation.


Caries and adolescents.
The rapid improvement in oral health conditions in childhood and adolescence and the ceaseless bombardment of information from the mass media have, during little more than 30 years, brought about a decrease in the prevalence of caries of more than 70% in most European Union countries. The study aimed to take an accurate picture of oral health conditions and dental prevention habits among adolescents. The research was conducted on a group of 340 adolescents (12-16 years) in the province of Bologna (Imola) and used the SPSS to compare clinical and epidemiological parameters with medical-history data traditionally understood to be determinant for caries. From an analysis of the data it emerged that the mean value of the decay, missing or filled tooth (DMFT) index in the group was 1.8765 +/- 2.1987 and that the plaque index (according to Löe and Silness) was 1.2519 +/- 0.4213. Crossing the data obtained, a highly significant correlation emerged (P=0.004) between plaque and caries indexes, and confirmed the primary role of bacterial plaque in causing caries. Unlike what we expected and unlike data reported in the international literature, the caries index was not found to be correlated in a statistically significant way with frequency of brushing, ''preferential consumption of sweet snacks'' (P=0.231) nor ''eating sweets and chewing gum'' (P=0.159) or with taking fluoride tablets (P=0.406). The key to success during adolescence is rooted in childhood; it is the pediatricians' and parents' job to guide and control the acquisition of correct dietary and oral hygiene habits.


Ultrasensitive Detection and Separation of Pancreatic Cancer Biomarker CA 19-9 Using a Multiphoton Laser Wave-Mixing Detector Interfaced to Capillary Electrophoresis.
The carbohydrate antigen 19-9 (CA 19-9) is the most commonly used biomarker in the clinical diagnosis of pancreatic cancer. Multiphoton nonlinear laser wave-mixing spectroscopy is presented as an ultrasensitive detection method for CA 19-9. Wave mixing is an optical absorption-based method, and hence, one can detect CA 19-9 without labels in their native form using compact ultraviolet (UV) lasers or labeled samples using a visible laser. The wave-mixing signal exhibits a quadratic dependence on the sample concentration, and hence, it is an ideal sensor to monitor small changes in the sample. Wave mixing has inherent advantages over other absorption-based detection methods, including short optical path length (micrometer-thin samples instead of 1 cm cuvette) and excellent spatial resolution (micrometer probe). Since the laser wave-mixing probe volume is small (picoliter), it is convenient to interface to microfluidics or capillary-based electrophoresis systems to enhance chemical specificity. Our wave-mixing detectors could be configured as portable battery-powered devices suitable for field use. Laser wave-mixing spectroscopy offers enhanced selectivity levels for protein detection when coupled with capillary electrophoresis (CE). We report a concentration detection limit of 0.16 U/mL, and a corresponding mass detection limit of 1.2 × 10-8 U, and these detection limits are better than those of chemiluminescence- or ELISA- based methods.


Studies on the energetic metabolism of Shigella flexneri times Escherichia coli hybrids devoid of penetration ability I. Glycolysis.
The aerobic and anaerobic (in presence of KCN) glycolysis is studied of avirulent hybrids of Shigella flexneri according to the keratoconjunctivitis test of Sereny with genetic characteristics lac-+kcp-minus devoid of penetration ability. It is established that lac-+kcp-minus hybrids which have lost their ability to penetrate the cells due to replacement of KCP-gene of the chromosome of donor strain E. coli K-12 P4 times, are characterized with a steep decrease of their glycolitic activity in both aerobic and anaerobic conditions. The data shows that the loss of penetrate ability of the Shigella flexneri hybrids correlates with the decrease of their glycolitic ability.


Visualization of nonvascular cranial tumor in cerebral flow study: case report.
Unusual results were obtained from a cerebral blood flow study and a brain scan performed on a patient with an uncommon, nonvascular scalp tumor eventually identified as a proliferating trichilemmal cyst with acanthosis. The tumor accumulated the radionuclide during the early phase of the cerebral flow study, and the increased radioactivity was persistent, being prominently observable in a scan made 3 min and 2 hr after the radionuclide injection. This unusual, positive finding in a cerebral blood flow study of a nonvascular tumor was thought to be a consequence of the higher counting efficiency resulting from the lack of shielding by the skull and from the larger volume of the tumor tissue.


Colorizing the Past: Deep Learning for the Automatic Colorization of Historical Aerial Images.
The colorization of grayscale images can, nowadays, take advantage of recent progress and the automation of deep-learning techniques. From the media industry to medical or geospatial applications, image colorization is an attractive and investigated image processing practice, and it is also helpful for revitalizing historical photographs. After exploring some of the existing fully automatic learning methods, the article presents a new neural network architecture, Hyper-U-NET, which combines a U-NET-like architecture and HyperConnections to handle the colorization of historical black and white aerial images. The training dataset (about 10,000 colored aerial image patches) and the realized neural network are available on our GitHub page to boost further research investigations in this field.


Hormonal regulation of phospholipid methyltransferase by 3',5'-cyclic adenosine monophosphate-dependent and independent mechanisms.
Treatment of isolated rat adipocytes with epinephrine or isoproterenol caused a time- and concentration-dependent increase in phospholipid methyltransferase (PLMT) activity that was blocked by propranolol and unaffected by phentolamine. Forskolin mimicked the stimulatory effect on PLMT, and insulin inhibited this effect. In both the absence and presence of insulin, there was a linear relationship between PLMT activity and lipolysis. PLMT activity was also increased in response to oxytocin, which does not activate adenylate cyclase in adipocytes and does not stimulate lipolysis. The effects of oxytocin were inhibited by insulin and were additive with those of isoproterenol on PLMT. These data support the hypothesis that in adipocytes, PLMT is activated by a cAMP-dependent protein kinase and a cAMP-independent mechanism, both of which can be regulated independently, and both of which are sensitive to inhibition by insulin.


Osteopontin contributes to effective neutrophil recruitment, IL-1β production and apoptosis in Aspergillus fumigatus keratitis.
Fungal keratitis is a major cause of corneal ulcers, resulting in significant visual impairment and blindness. A phosphorylated glycoprotein secreted by immunocompetent cells, osteopontin (OPN) mediates cluster formation of the host fungal receptors and enhances the phagocytosis and clearance of pathogenic fungi. However, whether OPN production and function occurs in fungal keratitis is unknown. OPN expression in Aspergillus fumigatus keratitis patient corneas was assessed by quantitative polymerase chain reaction (qRT-PCR) and immunofluorescence. Human neutrophils, THP-1 macrophages and corneal epithelial cells (HCECs) stimulated with A. fumigatus were utilized for in vitro experiments. Mouse models of A. fumigatus keratitis were developed by intrastromal injection for in vivo experiments. Using siRNAs, neutralizing antibodies, recombinant proteins and inhibitors, the production and role of OPN in A. fumigatus infection was assessed by clinical evaluation, qRT-PCR, immunofluorescence, western blotting and bioluminescence image acquisition. We observed increased corneal OPN expression in A. fumigatus keratitis patients and mouse models compared to controls. OPN production in response to A. fumigatus infection was dependent on LOX-1 and Erk1/2. Compared to controls, OPN knockdown impaired proinflammatory cytokine IL-1β production, which was dependent on 4E-BP1. OPN knockdown decreased myeloperoxidase levels, and resulted in decreased neutrophil recruitment, higher fungal load and increased apoptosis in mouse A. fumigatus keratitis. Our results indicate that OPN is a critical component of the antifungal immune response and is essential for effective neutrophil recruitment, inflammatory cytokine production and apoptosis in A. fumigatus keratitis.


Secretion of major adrenal androgens following ACTH administration in obese women with different body fat distribution.
To investigate whether obese female subjects with abdominal obesity may have adrenal androgen hypersecretion, we examined two groups of women with abdominal (n = 12) and peripheral (n = 13) obesity (defined by body mass index and waist-to-hip ratio) and a group of seven healthy normal-weight women. All subjects underwent the following protocol study that included a) baseline determination of major adrenal androgens, b) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microg/Kg BW, e.v.), at 90 min intervals, with blood samples taken for cortisol and androgens, c) an oral glucose tolerance test, performed by administering glucose (75 gr), with blood samples taken for glucose and insulin determination. Each woman also underwent a control saline study. We then investigated the relationships between basal and stimulated androgen levels, body weight and fat distribution and fasting and stimulated insulin levels. Although basal cortisol levels were similar, their increase (as AUC) after the ACTH test was higher in women with abdominal obesity than in the other groups. On the contrary, there were no significant differences in basal and stimulated serum levels of dehydroepiandrosterone, androstenedione and 17-hydroxyprogesterone among the three groups. Fasting and stimulated (as AUC) insulin levels were significantly higher (p < 0.05) in women with abdominal obesity than in those with peripheral obesity and controls. No significant correlation was present between basal and stimulated androgen levels and body mass index, the waist-to-hip ratio or basal and stimulated cortisol values. Therefore, our data indicate that adrenal androgen secretion following low-dose ACTH administration in premenopausal women does not seem to be a function of body fat mass, fat distribution and insulin levels, nor does it correlate with the capacity of the adrenal glands to secrete cortisol in both basal and stimulated conditions.


Enhanced activity of the myocardial Na+/H+ exchanger NHE-1 contributes to cardiac remodeling in atrial natriuretic peptide receptor-deficient mice.
Atrial natriuretic peptide (ANP), through its guanylyl cyclase-A (GC-A) receptor, not only is critically involved in the endocrine regulation of arterial blood pressure but also locally moderates cardiomyocyte growth. The mechanisms underlying the antihypertrophic effects of ANP remain largely uncharacterized. We examined the contribution of the Na+/H+ exchanger NHE-1 to cardiac remodeling in GC-A-deficient (GC-A(-/-)) mice. Fluorometric measurements in isolated adult cardiomyocytes demonstrated that cardiac hypertrophy in GC-A(-/-) mice was associated with enhanced NHE-1 activity, alkalinization of intracellular pH, and increased Ca2+ levels. Chronic treatment of GC-A(-/-) mice with the NHE-1 inhibitor cariporide normalized cardiomyocyte pH and Ca2+ levels and regressed cardiac hypertrophy and fibrosis, despite persistent arterial hypertension. To characterize the molecular pathways driving cardiac hypertrophy in GC-A(-/-) mice, we evaluated the activity of 4 prohypertrophic signaling pathways: the mitogen-activated protein kinases (MAPK), the serine-threonine kinase Akt, calcineurin, and Ca2+/calmodulin-dependent kinase II (CaMKII). The results demonstrate that all 4 pathways were activated in GC-A(-/-) mice, but only CaMKII and Akt activity regressed during reversal of the hypertrophic phenotype by cariporide treatment. In contrast, the MAPK and calcineurin/NFAT signaling pathways remained activated during regression of hypertrophy. On the basis of these results, we conclude that the ANP/GC-A system moderates the cardiac growth response to pressure overload by preventing excessive activation of NHE-1 and subsequent increases in cardiomyocyte intracellular pH, Ca2+, and CaMKII as well as Akt activity.


Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.
Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucella infection. Using knockout dermal fibroblasts, we confirmed its role for Brucella but found that it is not required for Salmonella infection. CD98hc transiently accumulates around the bacteria during the early phases of infection and is required for both optimal bacterial uptake and intracellular multiplication of Brucella. These results provide new insights into the complex interplay between Brucella and its host.


Effect of spin relaxations on the spin mixing conductances for a bilayer structure.
The spin current can result in a spin-transfer torque in the normal-metal(NM)-ferromagnetic-insulator(FMI) or normal-metal(NM)-ferromagnetic-metal(FMM) bilayer. In the earlier study on this issue, the spin relaxations were ignored or introduced phenomenologically. In this paper, considering the FMM or FMI with spin relaxations described by a non-Hermitian Hamiltonian, we derive an effective spin-transfer torque and an effective spin mixing conductance in the non-Hermitian bilayer. The dependence of the effective spin mixing conductance on the system parameters (such as insulating gap, s-d coupling, and layer thickness) as well as the relations between the real part and the imaginary part of the effective spin mixing conductance are given and discussed. We find that the effective spin mixing conductance can be enhanced in the non-Hermitian system. This provides us with the possibility to enhance the spin mixing conductance.


Computed tomographic lymphangiography via intra-metatarsal pad injection is feasible in dogs with chylothorax.
Lymphangiography can be useful for preoperative planning in chylothorax. Conventional ultrasound-guided intranodal injection can be difficult in some cases and is dependent upon operator skill. Alternative methods have been proposed to simplify the procedure, but their feasibility has not been sufficiently evaluated in clinical cases. The primary purpose of this multicenter, retrospective, descriptive study was to assess the feasibility and describe the clinical findings of CT lymphangiography by intrametatarsal pad injection in dogs with naturally occurring chylothorax. Twenty dogs were analyzed, and enhancement of thoracic ducts (TDs) was successful in 18 (90%) dogs within 5-14 min after initiating the injection, while successful enhancement of the lymphatic vessels cranial to the popliteal lymph nodes was seen in all dogs within 5 min after injection. The dose with good success to achieve TD enhancement was 1 mL/kg (concentration 350 mg I/kg). Only two dogs had mild discomfort after recovery from general anesthesia. Computed tomography lymphangiography by intrametatarsal pad injection is a feasible, easy, and safe procedure, which could provide adequate TD and cisterna chyli enhancement, identify TD number and cisterna chyli location and structure, and contribute to surgical planning.


Assessing Molecular Point-of-Care Testing and Dried Blood Spot for Hepatitis C Virus Screening in People Who Inject Drugs.
Injecting drug use is a major driver of hepatitis C virus (HCV) spread worldwide, and the World Health Organization (WHO) has identified people who inject drugs (PWID) as a key population to target for HCV screening and care. Point-of-care (POC) hepatitis C tests and dried blood spot (DBS) sampling offer benefits for the management of patients with HCV infection by increasing HCV testing and linkage to care in different nonclinical settings. The aims of this prospective study were to evaluate the feasibility and the acceptability of use HCV ribonucleic acid (RNA) POC and fingerstick DBS testing in social-medical risk-reduction centers and to describe the cascade of care among PWID in France. Between June 2018 and February 2019, 89 consecutive HCV-seropositive PWID attending 2 drug treatment services and 1 supervised consumption room in inner Paris were invited to participate in further evaluation, undergoing a clinical review with a liver assessment and blood tests including fingerstick capillary whole blood POC HCV RNA testing and fingerstick DBS sampling. Of the 89 participants enrolled, HCV RNA was detected in 34 (38.6%) participants. Fingerstick whole blood POC RNA testing and HCV RNA detection from DBS sample were feasible and acceptable among PWID with no major difference in terms of HCV RNA detection rate. Overall, 16 participants received pan-genotypic antiviral treatment. The proportion of PWID with sustained virologic response at 12 weeks was 81.2%, with data for 3 patients still pending. One-step screening strategy based on the detection of HCV RNA would engage people in care for treatment scale-up and HCV elimination.


Moderating the morbidity of divorce.
Divorce is frequent in our society. It is a "marker" of high stress periods that precede and follow it. The events surrounding it have clear negative effects on the physical and mental health of all those involved. The issues and the reactions, different for fathers and mothers and for children, are determined by the sex and developmental stage. The effects are interactive and events subsequent to the divorce influence the restoration of competent functioning. This paper examines these differential effects, methods of helping in the resolution process and opportunities of preventive work with this high risk population.


Neuronal polarization: From spatiotemporal signaling to cytoskeletal dynamics.
Neuronal polarization establishes distinct molecular structures to generate a single axon and multiple dendrites. Studies over the past years indicate that this efficient separation is brought about by a network of feedback loops. Axonal growth seems to play a major role in fueling those feedback loops and thereby stabilizing neuronal polarity. Indeed, various effectors involved in feedback loops are pivotal for axonal growth by ultimately acting on the actin and microtubule cytoskeleton. These effectors have key roles in interconnecting actin and microtubule dynamics - a mechanism crucial to commanding the growth of axons. We propose a model connecting signaling with cytoskeletal dynamics and neurite growth to better describe the underlying processes involved in neuronal polarization. We will discuss the current views on feedback loops and highlight the current limits of our understanding.


Research for universal health coverage: setting priorities for policy and systems research in Uganda.
There is international consensus on the need for countries to work towards achieving universal health coverage (UHC) whereby the population is given access to all appropriate promotive, preventive, curative and rehabilitative services at affordable cost. The World Health Organisation (2013) urges all countries to undertake research to customise UHC within national development agendas. To describe the process used to prioritise UHC within the health systems research and development agenda in Uganda. Two national consultative workshops were convened in May and August 2015 to develop a UHC research agenda in Uganda. The participants included multisector representatives from local, national, and international organisations. A participatory approach with structured deliberations and multi-voting techniques was used. Stakeholders' views were analysed thematically according to health systems building blocks, and multi-voting was used to assign priorities across themes and sub-themes. The priorities were further validated and disseminated at national health sector meetings. Of the 80 invited stakeholders, 57 (71.3%) attended. The expressed priorities were: 1) health workforce; 2) governance; 3) financing; 4) service delivery, and 5) community health. The participants also recommended crosscutting research themes to address the social determinants of health, multisectoral collaboration, and health system resilience to protect against external shocks and disease epidemics. Discussions that capture the diverse perspectives of stakeholders provide a way of exploring UHC within health policy and systems development. In Uganda, attention should be paid to the principal challenges of mobilising financial and technical capabilities for research and strengthening the link between evidence generation and policy actions to achieve UHC.


Enterotoxins, colonization factors and serotypes of enterotoxigenic Escherichia coli from humans and animals.
Enterotoxigenic Escherichia coli (ETEC) strains may synthesize both thermolabile (LT-I and LT-II) and thermostable (STa and STb) enterotoxins. Whereas thermolabile enterotoxins are high molecular weight proteins (85,000 d-90,000 d) composed by a single enzymatic A subunit combined with five B subunits which enable toxin for the receptor recognition, thermostable enterotoxins are small peptide chains with molecular weight between 1,900 d and 5,000 d. In addition to the synthesis of enterotoxins, the ability of ETEC strains to cause diarrhoea is also conditioned by the possession of colonization factors which enable bacteria adhere-to and colonize the luminal surface of small bowel. Colonization factors in ETEC strains were located in rigid fimbriae and flexible fibrils constituted by protein subunits ranging in size from 14,500 d to 31,000 d and usually responsible for mannose-resistant haemagglutination with determined erythrocyte species. Both enterotoxins and colonization factors are controlled by plasmids. There exist plasmids which may code separately enterotoxins and colonization factors, and besides there also exist recombinant plasmids coding together these two virulence factors. Human ETEC strains may synthesize LT-I and/or STa enterotoxins, they may possess the colonization factors named CFA/I, CFA/II, CFA/III or CFA/IV, and they belong mainly to serogroups O6, O8, O15, O20, O25, O27, O63, O77, O78, O114, O115, O126, O128, O139, O148, O153, O159 and O167. ETEC strains from porcine origin synthesize LT-I, STa and/or STb, they possess the colonization factors K88, P987, K99 or F41, and they usually belong to serogroups O8, O9, O20, O45, O64, O101, O115, O138, O141, O147, O149 and O157. Bovine and ovine ETEC strains are usually STa producers harbouring on the bacterial surface K99 or F41 colonization factors and they belong to serogroups O8, O9 and O101. Nevertheless, some particular bovine ETEC strains synthesizing LT-II have been described. Thus, a high specificity level between ETEC strains causing diarrhoea in humans and domestic animals can be observed. This is mainly due to the specific recognition between bacterial colonization factors and the epithelial receptors during host-parasite interaction.


Does PtaRHE1, a poplar RING-H2 protein, play a role in water conduction through ABA signaling?
RING (REALLY INTERESTING NEW GENE) proteins with E3 ligase activity are largely represented in plants. They have been shown to play important roles in the regulation of many biological processes by recognizing target proteins for ubiquitination. PtaRHE1, encoding a poplar RING-H2 domain-containing protein with E3 ligase activity has been previously shown to be expressed during the establishment of secondary vascular system in poplar. In the present report, we demonstrate that the expression of PtaRHE1 and the accumulation of its corresponding protein are modulated by the relative atmospheric and soil humidity and by abscisic acid. Overall, the integrated data are discussed within a working model highlighting a plausible function of PtaRHE1 in the signaling and/or in the regulation of water status in poplar.


Renal Squamous Cell Carcinoma with Staghorn Calculus.
A 70-year-old Japanese woman was referred to our department due to general fatigue and a persistent low fever. We performed percutaneous nephrostomy and administered antibiotics for the pyelonephritis due to her left staghorn calculus. After the infection had been brought under control and her general condition improved, we performed nephrectomy. A pathologic examination revealed renal squamous cell carcinoma (SCC) in addition to xanthogranulomatous inflammation. Seventeen days after the operation, computed tomography demonstrated local recurrence of the tumor; therefore, she received palliative care. Two months after her operation, she died of renal SCC.


CT and MR Imaging Appearance of the Pedicled Submandibular Gland Flap: A Potential Imaging Pitfall in the Posttreatment Head and Neck.
Pedicled locoregional submandibular gland reconstruction flaps are increasingly used in oncologic head and neck surgery and have unique imaging characteristics that can mimic locally recurrent tumor. In this clinical report, 23 posttreatment imaging studies were evaluated in 19 patients who had undergone submandibular gland flap reconstructions after resection of a primary head and neck tumor. Submandibular gland flaps were most commonly mobilized into the parapharyngeal space or parotid bed, with others located inferior to the mandibular body and within marginal mandibulectomy defects. The original shape of the gland was typically not preserved. Identifying the submandibular gland hilum, vascular pedicle, glandular texture, and absence of submandibular gland in the orthotopic location was most useful in recognizing a flap. The interpreting radiologist must be familiar with the unique submandibular gland flap imaging characteristics to accurately differentiate normal postoperative appearance and recurrent tumor.


Neurobiology of periventricular leukomalacia in the premature infant.
Brain injury in the premature infant is a problem of enormous importance. Periventricular leukomalacia (PVL) is the major neuropathologic form of this brain injury and underlies most of the neurologic morbidity encountered in survivors of premature birth. Prevention of PVL now seems ultimately achievable because of recent neurobiologic insights into pathogenesis. The pathogenesis of this lesion relates to three major interacting factors. The first two of these, an incomplete state of development of the vascular supply to the cerebral white matter, and a maturation-dependent impairment in regulation of cerebral blood flow underlie a propensity for ischemic injury to cerebral white matter. The third major pathogenetic factor is the maturation-dependent vulnerability of the oligodendroglial (OL) precursor cell that represents the major cellular target in PVL. Recent neurobiologic studies show that these cells are exquisitely vulnerable to attack by free radicals, known to be generated in abundance with ischemia-reperfusion. This vulnerability of OLs is maturation-dependent, with the OL precursor cell highly vulnerable and the mature OL resistant, and appears to relate to a developmental window characterized by a combination of deficient antioxidant defenses and active acquisition of iron during OL differentiation. The result is generation of deadly reactive oxygen species and apoptotic OL death. Important contributory factors in pathogenesis interact with this central theme of vulnerability to free radical attack. Thus, the increased likelihood of PVL in the presence of intraventricular hemorrhage could relate to increases in local iron concentrations derived from the hemorrhage. The important contributory role of maternal/fetal infection or inflammation and cytokines in the pathogenesis of PVL could be related to effects on the cerebral vasculature and cerebral hemodynamics, to generation of reactive oxygen species, or to direct toxic effects on vulnerable OL precursors. A key role for elevations in extracellular glutamate, caused by ischemia-reperfusion, is suggested by demonstrations that glutamate causes toxicity to OL precursors by both nonreceptor- and receptor-mediated mechanisms. The former involves an exacerbation of the impairment in antioxidant defenses, and the latter, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor-mediated cell death. Most importantly, these new insights into the pathogenesis of PVL suggest potential preventive interventions. These include avoidance of cerebral ischemia by detection of infants with impaired cerebrovascular autoregulation, e.g. through the use of in vivo near-infrared spectroscopy, the use of free radical scavengers to prevent toxicity by reactive oxygen species, the administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor antagonists to prevent glutamate-mediated injury, or the use of maternal antibiotics or anticytokine agents to prevent toxicity from maternal/fetal infection or inflammation and cytokines.


[Functional colon sonography in neuronal intestinal dysplasia. Report of 3 cases].
For the first time morphology and function of the colon were analysed by sonography in three children with M. Hirschsprung and neuronal-intestinal dysplasia. After one year two children attained almost normalisation of colon-peristalsis in the nonaganglionic segments. A resection of the neuronal-dysplastic segments was not necessary. In one child there was seen no change of the distal colon motility. The limit of resection at operation was determined by sonographic diagnosis following observation of stimulated motility. Sonographic long-time examination in connection with medicamental stimulation of the colon allows determination on timing and kind of therapy in neuronal-intestinal dysplasia.