Determination of the critical diabetes duration in a streptozotocin-induced diabetic rat calvarial defect model for experimentation regarding bone regeneration.
The purpose of this study was to determine the critical diabetes duration in a streptozotocin (STZ)-induced diabetic rat calvarial defect model for experimentation regarding bone regeneration by evaluating the association between diabetes duration and bone healing capacity through histological and radiographic analyses. Experimental diabetes was induced in 50 of 60 rats by an STZ injection. The rats were divided into 5 groups, including a control group (group 1), according to diabetes durations of 0, 2, 4, 6, and 8 weeks, respectively. Eighteen rats survived: 4 in group 1, 4 in group 2, 4 in group 3, 5 in group 4, and 1 in group 5. Calvarial defects were created at 0, 2, 4, 6, and 8 weeks after STZ injection in groups 1-5. Cone-beam computed tomography scanning was performed at baseline and at 5 and 7 weeks after surgery. The rats were sacrificed 7 weeks after surgery, followed by histological evaluation. The voxel gray values (VGVs) of group 1 and group 2 increased, whereas the VGVs of group 3 and group 4 decreased starting 5 weeks after surgery, although this trend did not reach statistical significance between groups. On the reconstructed 3-dimensional images and based on an analysis of histological features, groups 1 and 2 showed apparent bone regeneration, while groups 3-5 showed very limited bone regeneration. The critical diabetes duration in an STZ-induced diabetic rat calvarial defect model for experimentation regarding bone regeneration was between 2 and 4 weeks. It is suggested that researchers who use STZ-induced diabetic rats wait for more than 2 weeks following diabetes induction before placing implants or conducting bone regeneration studies to allow definite disturbances in bone healing to emerge.


Inverse relationship between trk expression and N-myc amplification in human neuroblastomas.
We examined the expression of the trk protooncogene in a series of 82 neuroblastomas to determine its relationship to N-myc amplification and expression, disease stage, patient age, and survival. We found that virtually all stage I, II, and IV-S patients had moderate to high levels of trk expression, whereas most advanced stage neuroblastomas had low or absent levels. All but one tumor with N-myc amplification had low or absent trk expression, and the one exception was regressing at the time it was resected. Conversely, all neuroblastomas identified by mass screening had moderate to high expression of trk, and all these patients are surviving. Thus, trk expression was associated with an absence of N-myc amplification, lower disease stage, lower patient age, and favorable outcome. Tumors with high trk expression may be more likely to differentiate, regress spontaneously, or respond well to therapy.


Local and cortical effects of olfactory bulb lesions on trophic support and cholinergic function and their modulation by estrogen.
This study determined whether olfactory bulb lesions would affect trophic support to its afferent, the horizontal limb of the diagonal band of Broca (hIDBB), and if estrogen would ameliorate the effects of neural injury in this circuit. NMDA injections into the olfactory bulb resulted in neural injury as indicated by cell loss and increased glial fibrillary acidic protein immunoreactivity. Olfactory bulb lesions severely reduced BDNF expression in its afferent, the hIDBB, while NGF was only reduced in lesioned animals deprived of estrogen. In the olfactory bulb itself, lesions increased BDNF expression, but not NGF. Paradoxically, bulb lesions up-regulated both NGF and BDNF in another target of the hIDBB, the cingulate cortex. Moreover, olfactory bulb lesions affected choline uptake and ChAT activity locally, as well as in the cingulate cortex. Estrogen significantly attenuated the lesion-induced loss of choline uptake in the cingulate cortex, but not at the primary lesion site. Collectively, these results indicate that neural injury to one limb of the forebrain cholinergic system may result in collateral damage to other limbs of this system, suggesting a mechanism for the progression of neurodegenerative diseases, such as Alzheimer's disease, that involve the cholinergic system. Furthermore, these data also indicate that estrogen selectively attenuates certain lesion-induced deficits.


Dictyosome-endoplasmic reticulum associations in higher plant cells? A serial-section analysis.
Serial sections through permanganate and glutaraldehyde/osmium fixed dictyosomes from suspension cultured sycamore cells and maize root cap cells have been analyzed. The results may be summarized as follows. For both sycamore and maize dictyosomes are: 1. transition vesicles between ER and dictyosome, and therefore a "forming face" to the dictyosome, not present. 2. direct, tubular ER-cisternal connections doubtful, if at all present; 3. "Maturing faces" to dictyosomes, i.e. a polarity in terms of the pinching-off of secretory vesicles, not a typical feature; 4. two types of vesicle associated with the dictyosome: large and small (in part "coated"); 5. cisternae present as a flattened, continuous central portion at whose periphery an extensive, anastomosing tubule system exists; 6. cisternae in the dictyosome stack not concentrically arranged, but lie somewhat displaced to one another. A characteristic feature of maize dictyosomes, in addition, is a bi- or unilateral distribution of hypertrophied slime vesicles. The kidney-shaped slime vesicles are arranged opposite to one another at the tubular periphery of a cisternae; the region in between is occupied with smaller, occasionally coated, vesicles. It would appear from these results that the endomembrane concept sensu strictu [58] is not applicable to higher plant cells whose main secretory product is polysaccharide rather than protein. Consequences and alternatives in relation to membrane-flow in such cells are discussed.


Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials.
A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women could enhance autologous virus neutralization and thereby reduce this risk of vertical HIV transmission. Here, we assessed autologous virus NAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) protocols 104 and 102, representing historical phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines administered to HIV-infected pregnant women (ClinicalTrials registration no. NCT00001041). Maternal HIV Env-specific plasma binding and neutralizing antibody responses were characterized before and after vaccination in 15 AVEG 104 (n = 10 vaccine recipients, n = 5 placebo recipients) and 2 AVEG 102 (n = 1 vaccine recipient, n = 1 placebo recipient) participants. Single-genome amplification (SGA) was used to obtain HIV env gene sequences of autologous maternal viruses for pseudovirus production and neutralization sensitivity testing in pre- and postvaccination plasma of HIV-infected pregnant vaccine recipients (n = 6 gp120, n = 1 gp160) and placebo recipients (n = 3). We detected an increase in Env subunit MN gp120-specific IgG binding in the group of vaccine recipients between the first immunization visit and the last visit at delivery (P = 0.027, 2-sided Wilcoxon test). While no difference was observed in the levels of autologous virus neutralization potency between groups, in both groups maternal plasma collected at delivery more effectively neutralized autologous viruses from early pregnancy than late pregnancy. Immunization strategies capable of further enhancing these autologous virus NAb responses in pregnant women will be important to block vertical transmission of HIV.IMPORTANCE Maternal antiretroviral therapy (ART) has effectively reduced but not eliminated the burden of mother-to-child transmission of HIV across the globe, as an estimated 160,000 children were newly infected with HIV in 2018. Thus, additional preventive strategies beyond ART will be required to close the remaining gap and end the pediatric HIV epidemic. A maternal active immunization strategy that synergizes with maternal ART could further reduce infant HIV infections. In this study, we found that two historic HIV Env vaccines did not enhance the ability of HIV-infected pregnant women to neutralize autologous viruses. Therefore, next-generation maternal HIV vaccine candidates must employ alternate approaches to achieve potent neutralizing antibody and perhaps nonneutralizing antibody responses to effectively impede vertical virus transmission. Moreover, these approaches must reflect the broad diversity of HIV strains and widespread availability of ART worldwide.


Effectiveness in improving knowledge, practices, and intakes of "key problem nutrients" of a complementary feeding intervention developed by using linear programming: experience in Lombok, Indonesia.
Complementary feeding recommendations (CFRs) with the use of locally available foods can be developed by using linear programming (LP). Although its potential has been shown for planning phases of food-based interventions, the effectiveness in the community setting has not been tested to our knowledge. We aimed to assess effectiveness of promoting optimized CFRs for improving maternal knowledge, feeding practices, and child intakes of key problem nutrients (calcium, iron, niacin, and zinc). A community-intervention trial with a quasi-experimental design was conducted in East Lombok, West Nusa Tenggara Province, Indonesia, on children aged 9-16 mo at baseline. A CFR group (n = 240) was compared with a non-CFR group (n = 215). The CFRs, which were developed using LP, were promoted in an intervention that included monthly cooking sessions and weekly home visits. The mother's nutrition knowledge and her child's feeding practices and the child's nutrient intakes were measured before and after the 6-mo intervention by using a structured interview, 24-h recall, and 1-wk food-frequency questionnaire. The CFR intervention improved mothers' knowledge and children's feeding practices and improved children's intakes of calcium, iron, and zinc. At the end line, median (IQR) nutrient densities were significantly higher in the CFR group than in the non-CFR group for iron [i.e., 0.6 mg/100 kcal (0.4-0.8 mg/100 kcal) compared with 0.5 mg/100 kcal (0.4-0.7 mg/100 kcal)] and niacin [i.e., 0.8 mg/100 kcal (0.5-1.0 mg/100 kcal) compared with 0.6 mg/100 kcal (0.4-0.8 mg/100 kcal)]. However, median nutrient densities for calcium, iron, niacin, and zinc in the CFR group (23, 0.6, 0.7, and 0.5 mg/100 kcal, respectively) were still below desired densities (63, 1.0, 0.9, and 0.6 mg/100 kcal, respectively). The CFRs significantly increased intakes of calcium, iron, niacin, and zinc, but nutrient densities were still below desired nutrient densities. When the adoption of optimized CFRs is constrained by economic access for or acceptability of nutrient-dense foods, other strategies need to be incorporated into interventions to ensure adequate intakes of these nutrients.


Mechanisms for the activation of Toll-like receptor 2/4 by saturated fatty acids and inhibition by docosahexaenoic acid.
Saturated fatty acids can activate Toll-like receptor 2 (TLR2) and TLR4 but polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA) inhibit the activation. Lipopolysaccharides (LPS) and lipopetides, ligands for TLR4 and TLR2, respectively, are acylated by saturated fatty acids. Removal of these fatty acids results in loss of their ligand activity suggesting that the saturated fatty acyl moieties are required for the receptor activation. X-ray crystallographic studies revealed that these saturated fatty acyl groups of the ligands directly occupy hydrophobic lipid binding domains of the receptors (or co-receptor) and induce the dimerization which is prerequisite for the receptor activation. Saturated fatty acids also induce the dimerization and translocation of TLR4 and TLR2 into lipid rafts in plasma membrane and this process is inhibited by DHA. Whether saturated fatty acids induce the dimerization of the receptors by interacting with these lipid binding domains is not known. Many experimental results suggest that saturated fatty acids promote the formation of lipid rafts and recruitment of TLRs into lipid rafts leading to ligand independent dimerization of the receptors. Such a mode of ligand independent receptor activation defies the conventional concept of ligand induced receptor activation; however, this may enable diverse non-microbial molecules with endogenous and dietary origins to modulate TLR-mediated immune responses. Emerging experimental evidence reveals that TLRs play a key role in bridging diet-induced endocrine and metabolic changes to immune responses.


Effect of bis-glycinate bound zinc or zinc sulfate on zinc metabolism in growing lambs.
To assess the efficacy of bis-glycinate bound Zn, 36 crossbred wethers (34 ± 2 kg) were sorted by body weight into three groups and stagger started on a Zn-deficient diet (18 mg Zn/kg dry matter [DM]; 22.5% neutral detergent fiber [NDF]) for 45 d prior to a 15-d metabolism period (10 d adaptation and 5 d collection). On day 46, lambs were randomly assigned to dietary treatments (four lambs treatment-1group-1): no supplemental Zn (CON) or 15 mg supplemental Zn/kg DM (ZINC) as Zn sulfate (ZS) or bis-glycinate (GLY; Plexomin Zn, Phytobiotics). Blood was collected from all lambs on days 1, 44, 56, and 61. Liver, jejunum, and longissimus dorsi samples were collected after euthanasia on day 61. Gene expression was determined via quantitative real-time polymerase chain reaction. Data were analyzed using ProcMixed of SAS (experimental unit = lamb; fixed effects = treatment, group, and breed) and contrast statements assessed the effects of supplemental Zn concentration (ZINC vs. CON) and source (GLY vs. ZS). After 15 d of Zn supplementation, plasma Zn concentrations were greater for ZINC vs. CON and GLY vs. ZS (P ≤ 0.01); tissue Zn concentrations were unaffected (P ≥ 0.27). Liver Cu concentrations were lesser for ZINC vs. CON (P = 0.03). Longissimus dorsi Mn concentrations were greater for ZINC vs. CON (P = 0.05) and tended to be lesser for GLY vs. ZS (P = 0.09). Digestibility of DM, organic matter (OM), and NDF was lesser for ZINC vs. CON (P ≤ 0.05); acid detergent fiber digestibility tended to be greater for GLY vs. ZS (P = 0.06). Nitrogen retention (g/d) tended to be greater for GLY vs. ZS (P = 0.10), and N apparent absorption was lesser for ZINC vs. CON (P = 0.02). Zinc intake, fecal output, retention, and apparent absorption were greater for ZINC vs. CON (P ≤ 0.01). Apparent absorption of Zn was -5.1%, 12.8%, and 15.0% for CON, ZS, and GLY, respectively. Nitrogen and Zn retention and apparent absorption were not correlated for CON (P ≥ 0.14) but were positively correlated for ZINC (retention: P = 0.02, r = 0.52; apparent absorption: P < 0.01, r = 0.73). Intestinal expression of Zn transporter ZIP4 was lesser for ZINC vs. CON (P = 0.02). Liver expression of metallothionein-1 (MT1) tended to be greater for GLY vs. ZS (P = 0.07). Although Zn apparent absorption did not differ between sources (P = 0.71), differences in post-absorptive metabolism may be responsible for greater plasma Zn concentrations and liver MT1 expression for GLY-supplemented lambs, suggesting improved bioavailability of GLY relative to ZS.


Prenotification but not envelope teaser increased response rates in a bulimia nervosa mental health literacy survey: A randomized controlled trial.
Understanding attitudes to mental health issues can inform public health interventions. However, low response rates may contribute to nonresponse bias. In a randomized controlled trial we examined the effect of sending a prenotification postcard before the questionnaire and the placement of a short message on the survey envelope (teaser) on response rates to a mailed questionnaire about bulimia nervosa "mental health literacy". Questionnaires were mailed to 3,010 adults (50.6% female and 49.4% male) aged 18-65 years. In a 2 (pre-notification-present; absent) by 2 (teaser-present; absent) design, questionnaire recipients were randomly allocated to the experimental strategies. Outcomes considered were response rate, response time, and cost. The overall response rate was 22.0%. Significant main effects showed higher response rates for the use of prenotification (present = 23.6%; absent = 20.3%), among female participants, and older participants. A significant interaction of teaser by gender indicated lower response rates for men who received the teaser but not for women. Older participants returned the questionnaire more promptly than younger participants. Females-but not males-who received the teaser were slower to return the questionnaire. Higher response rates for participants receiving the postcard compensated for increased costs, particularly for males and older participants. Response rates to a mental health postal survey can be increased through the use of prenotification.


Isolation and characterization of an RNA ligase from HeLa cells.
An RNA ligase has been purified from HeLa cells, which catalyzes the intra- and intermolecular ligation of linear RNA substrates possessing 5'-hydroxyl and 2',3'-cyclic phosphate termini in the presence of ATP or dATP. In this reaction, the 2',3'-cyclic phosphate is incorporated into a 3'-5'-phosphodiester bond, in agreement with the findings of Filipowicz et al. [Filipowicz, W., Konarska, M., Gross, H. J. & Shatkin, A. J. (1983) Nucleic Acids Res. 11, 1405-1418]. The activity of the purified enzyme is dependent on the addition of ATP or dATP, a divalent cation (Mg2+), and 5'-hydroxyl, 2',3'-cyclic phosphate-terminated RNA substrates. No ligation occurs with the substrates OH(Up)10G(3')p or OH(Up)10G(2')p or with 5'-phosphate, 2',3'-cyclic phosphate-terminated oligoribonucleotides.


A paralog of a bacteriochlorophyll biosynthesis enzyme catalyzes the formation of 1,2-dihydrocarotenoids in green sulfur bacteria.
Chlorobaculum tepidum, a green sulfur bacterium, utilizes chlorobactene as its major carotenoid, and this organism also accumulates a reduced form of this monocyclic pigment, 1',2'-dihydrochlorobactene. The protein catalyzing this reduction is the last unidentified enzyme in the biosynthetic pathways for all of the green sulfur bacterial pigments used for photosynthesis. The genome of C. tepidum contains two paralogous genes encoding members of the FixC family of flavoproteins: bchP, which has been shown to encode an enzyme of bacteriochlorophyll biosynthesis; and bchO, for which a function has not been assigned. Here we demonstrate that a bchO mutant is unable to synthesize 1',2'-dihydrochlorobactene, and when bchO is heterologously expressed in a neurosporene-producing mutant of the purple bacterium, Rhodobacter sphaeroides, the encoded protein is able to catalyze the formation of 1,2-dihydroneurosporene, the major carotenoid of the only other organism reported to synthesize 1,2-dihydrocarotenoids, Blastochloris viridis Identification of this enzyme completes the pathways for the synthesis of photosynthetic pigments in Chlorobiaceae, and accordingly and consistent with its role in carotenoid biosynthesis, we propose to rename the gene cruI Notably, the absence of cruI in B. viridis indicates that a second 1,2-carotenoid reductase, which is structurally unrelated to CruI (BchO), must exist in nature. The evolution of this carotenoid reductase in green sulfur bacteria is discussed herein.


The Human Brain in Depth: How We See in 3D.
Human perception is remarkably flexible: We experience vivid three-dimensional (3D) structure under diverse conditions, from the seemingly random magic-eye stereograms to the aesthetically beautiful, but obviously flat, canvases of the Old Masters. How does the brain achieve this apparently effortless robustness? Using brain imaging we are beginning to discover how different parts of the visual cortex support 3D perception by tracing different computations in the dorsal and ventral pathways. This review concentrates on studies of binocular disparity and its combination with other depth cues. This work suggests that the dorsal visual cortex is strongly engaged by 3D information and is involved in integrating signals to represent the structure of viewed surfaces. The ventral cortex may store representations of object configurations and the features required for task performance. These differences can be broadly understood in terms of the different computational demands of reducing estimator variance versus increasing the separation between exemplars.


One-Year Old Dormant, "Non-culturable" Mycobacterium tuberculosis Preserves Significantly Diverse Protein Profile.
For adaptation to stressful conditions, Mycobacterium tuberculosis (Mtb) is prone to transit to a dormant, non-replicative state, which is believed to be the basis of the latent form of tuberculosis infection. Dormant bacteria persist in the host for a long period without multiplication, cannot be detected from biological samples by microbiological methods, however, their "non-culturable" state is reversible. Mechanisms supporting very long capacity of mycobacteria for resuscitation and further multiplication after prolonged survival in a dormant phase remain unclear. Using methods of 2D electrophoresis and MALDI-TOF analysis, in this study we characterized changes in the proteomic profile of Mtb stored for more than a year as dormant, non-replicating cells with a negligible metabolic activity, full resistance to antibiotics, and altered morphology (ovoid forms). Despite some protein degradation, the proteome of 1-year-old dormant mycobacteria retained numerous intact proteins. Their protein profile differed profoundly from that of metabolically active cells, but was similar to the proteome of the 4-month-old dormant bacteria. Such protein stability is likely to be due to the presence of a significant number of enzymes involved in the protection from oxidative stress (katG/Rv1908, sodA/Rv3846, sodC/Rv0432, bpoC/Rv0554), as well as chaperones (dnaJ1/Rv0352, htpG/Rv2299, groEL2/Rv0440, dnaK/Rv0350, groES/Rv3418, groEL1/Rv3417, HtpG/Rv2299c, hspX/Rv2031), and DNA-stabilizing proteins. In addition, dormant cells proteome contains enzymes involved in specific metabolic pathways (glycolytic reactions, shortened TCA cycle, degradative processes) potentially providing a low-level metabolism, or these proteins could be "frozen" for usage in the reactivation process before biosynthetic processes start. The observed stability of proteins in a dormant state could be a basis for the long-term preservation of Mtb cell vitality and hence for latent tuberculosis.


Genetic Comparison of Stemness of Human Umbilical Cord and Dental Pulp.
This study focuses on gene expression patterns and functions in human umbilical cord (UC) and dental pulp (DP) containing mesenchymal stem cells (MSCs). DP tissues were collected from 25 permanent premolars. UC tissue samples were obtained from three newborns. Comparative gene profiles were obtained using cDNA microarray analysis and the expression of tooth development-associated and MSC-related genes was assessed by the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Genes related to cell proliferation, angiogenesis, and immune responses were expressed at higher levels in UC, whereas genes related to growth factor and receptor activity and signal transduction were more highly expressed in DP. Although UC and DP tissues exhibited similar expression of surface markers for MSCs, UC showed higher expression of CD29, CD34, CD44, CD73, CD105, CD146, and CD166. qRT-PCR analysis showed that CD146, CD166, and MYC were expressed 18.3, 8.24, and 1.63 times more highly in UC, whereas the expression of CD34 was 2.15 times higher in DP. Immunohistochemical staining revealed significant differences in the expression of genes (DSPP, DMP1, and CALB1) related to odontogenesis and angiogenesis in DP. DP and UC tissue showed similar gene expression, with the usual MSC markers, while they clearly diverged in their differentiation capacity.


HaMYBA-HabHLH1 regulatory complex and HaMYBF fine-tune red flower coloration in the corolla of sunflower (Helianthus annuus L.).
Sunflowers are well-known ornamental plants, while sunflowers with red corolla are rare and the mechanisms underlying red coloration remain unclear. Here, a comprehensive analysis of metabolomics and transcriptomics on flavonoid pathway was performed to investigate the molecular mechanisms underlying the differential color formation between red sunflower Pc103 and two yellow sunflowers (Yr17 and Y35). Targeted metabolomic analysis revealed higher anthocyanin levels but lower flavonol content in Pc103 compared to the yellow cultivars. RNA-sequencing and phylogenetic analysis identified multiple genes involved in the flavonoid pathway, including series of structural genes and three MYB and bHLH genes. Specifically, HaMYBA and HabHLH1 were up-regulated in Pc103, whereas HaMYBF exhibited reduced expression. HaMYBA was found to interact with HabHLH1 in vivo and in vitro, while HaMYBF does not. Transient expression analysis further revealed that HabHLH1 and HaMYBA cooperatively regulate increased expression of dihydroflavonol 4-reductase (DFR), leading to anthocyanin accumulation. On the other hand, ectopic expression of HaMYBF independently modulates flavonol synthase (FLS) expression, but hindered anthocyanin production. Collectively, our findings suggest that the up-regulation of HaMYBA and HabHLH1, as well as the down-regulation of HaMYBF, contribute to the red coloration in Pc103. It offers a theoretical basis for improving sunflower color through genetic engineering.


Immediate loading of implants in the aesthetic zone: comparison between two placement timings.
Implant rehabilitation delivered in accordance with the traditional protocol has proven to be highly predictable and acceptable (1). Nevertheless, the application of immediate loading on post-extraction implants, especially for aesthetic zones, has now considerably increased (2). The aim of this work is to illustrate the immediate loading of implants placed in the aesthetic zone through tapered design fixtures with microgeometry of a high degree of porosity inserted at the same time or 4-8 weeks from dental avulsion (TSA® Advance, Phibo®). A total of 15 implant fixtures of which 8 at an interval of 4-8 weeks from extraction (type 2) and the remaining according to the immediate post-extraction technique (type 1) were positioned. All implants were prosthesized within 24 hours from the placement. Definitive crowns replaced provisional restorations after 20-24 weeks. After 4 and 12 months from implant insertion, the following parameters were assessed: X-ray image, pain, mobility or suppuration, soft tissue condition and aesthetic appearance. Percentage of osseointegration was 93.75%, and 53.5% of the osseointegrated fixtures was type 2. No statistically significant difference between the mean ISQ values for implants of type 1 and 2 both in the post-operative period and after 12 months was evident, indicating that the timing of insertion did not affect the achievement of stability for the implant fixtures tested in our study. Immediate post-extraction implants showed a greater propensity for gingival recession and a peri-implant radiolucency greater than those placed at an interval of 4-8 weeks. The values obtained for the PES/WES and the subjective evaluation of the analyzed sample showed the considerable aesthetic value and the high level of satisfaction guaranteed by the implant technique illustrated. Although well-designed, high quality, randomized clinical trials are still needed as well as the requirement to establish a common, complete, and reproducible index for the evaluation of aesthetic outcome, immediate/early placement and loading of a single TSA® Advance, Phibo® may be considered a valuable and predictable option in terms of implant success as well as hard and soft tissue stability.


Iterative Correction of Reference Nucleotides (iCORN) using second generation sequencing technology.
The accuracy of reference genomes is important for downstream analysis but a low error rate requires expensive manual interrogation of the sequence. Here, we describe a novel algorithm (Iterative Correction of Reference Nucleotides) that iteratively aligns deep coverage of short sequencing reads to correct errors in reference genome sequences and evaluate their accuracy. Using Plasmodium falciparum (81% A + T content) as an extreme example, we show that the algorithm is highly accurate and corrects over 2000 errors in the reference sequence. We give examples of its application to numerous other eukaryotic and prokaryotic genomes and suggest additional applications. The software is available at http://icorn.sourceforge.net


Factors influencing termination of resuscitative efforts in children: a comparison of pediatric emergency medicine and adult emergency medicine physicians.
To examine factors that influence termination of resuscitative efforts (TORE) and compare pediatric emergency medicine (PEM) and general emergency medicine (GEM) physicians regarding TORE in children. Cross-sectional survey. All physicians board-certified in PEM as of November 1993 and a random sample of board-certified GEM physicians listed in the 1993 American College of Emergency Physicians directory. Self-administered questionnaires were mailed to participants who were asked about experience providing pediatric cardiopulmonary resuscitation (CPR) and demographic information. We posed a series of management questions eliciting factors that influence TORE decision-making in single context and case scenario format. Specific emphasis was placed on the influence of time and epinephrine dosing. One hundred and sixty (70%) PEM and 127 (62%) GEM responded. These groups differed significantly in years of experience (PEM 8.2, GEM 11.8), urban practice setting (PEM 84%, GEM 32%) and number of pediatric cardiopulmonary resuscitations per year (PEM 10.6, GEM 4.8), P < 0.001 for all. There were no significant differences between groups regarding features pathognomonic of death. PEM were more likely to consider low blood pH and iatrogenic causes of arrest as factors influencing TORE; GEM were more likely to consider co-morbid conditions (P < 0.05 for all). Medians for time estimates of minimum minutes of pulselessness that influence TORE were: PEM 26 to 30 minutes, GEM 31 to 35 minutes for both prehospital and emergency department settings (P < 0.05 for each). Approximately 20% of all respondents did not place a strict limit on time of pulselessness when determining TORE. No difference was observed between groups regarding maximum doses of epinephrine used prior to TORE. However, fewer GEM (50%) than PEM (75%) utilize "high dose" epinephrine according to current Pediatric Advanced Life Support (PALS) guidelines (P < 0.05). PEM physicians were more than two times more likely to terminate resuscitative efforts if return of spontaneous circulation was not achieved by 25 minutes compared to GEM physicians for both prehospital time of pulselessness [odds ratio 2.1, 95% confidence interval (1.01, 4.5)] and emergency department time of pulselessness [odds ratio 2.2, confidence interval (1.1, 4.6)]. 1) Several laboratory and clinical factors significantly influence physician's decisions regarding TORE; 2) regardless of setting, time of pulselessness does appear to be an influential factor in determining when to terminate resuscitation in children for most physicians; 3) PEM physicians are more likely to terminate resuscitative efforts than are GEM physicians if return of spontaneous circulation is not achieved by 25 minutes; 4) a significant number of PEM and GEM physicians do not use high dose epinephrine in accordance with current PALS recommendations.


Memory performance and fMRI signal in presymptomatic familial Alzheimer's disease.
Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes.


Precision detection of liver metastasis by collagen-targeted protein MRI contrast agent.
The Liver is the most common organ for metastasis for various cancers, including uveal melanoma, the most common primary intraocular tumor. Uveal melanoma metastasizes to the liver in ~90% of patients, and results in death in almost all cases due to late detection and lack of effective treatment. There is a pressing unmet medical need to develop MRI contrast agents and imaging methodologies with desired sensitivity and specificity to overcome the high heterogeneous background and in vivo properties as well as reduced toxicity. Herein, we report the development of a collagen targeting protein contrast agent (ProCA32.collagen1), since collagen is a diagnostic biomarker and therapeutic target for many types of primary and metastatic cancers and the tumor microenvironment. In addition to a strong affinity to collagen I, ProCA32.collagen1 possesses high relaxivities (r1 and r2 are 68.0 ± 0.25 and 100.0 ± 0.32 mM-1 s-1 at 1.4 T, respectively, and 42.6 ± 1.0 and 217 ± 2.4 mM-1s-1 at 7.0 T per particle). ProCA32.collagen1 also has strong serum stability against degradation, resistance to transmetallation, and 102 and 1013-fold higher metal selectivity for Gd3+ over Ca2+ and Zn2+, respectively, compared to clinical contrast agents. ProCA32.collagen1 does not exhibit any cell toxicity for various cell lines. Sensitive detection of liver lesions in animal models can be achieved using multiple imaging methodologies, taking advantage of the dual relaxation property of ProCA32.collagen1. ProCA32.collagen1 enables sensitive and early stage detection of hepatic micrometastasis as small as 0.144 mm2 and two different tumor growth patterns. Further development of ProCA32.collagen1 has the potential to greatly facilitate non-invasive, early detection and staging of primary and metastatic liver cancers, and devising effective treatments.


Depth Map Super-Resolution Considering View Synthesis Quality.
Accurate and high-quality depth maps are required in lots of 3D applications, such as multi-view rendering, 3D reconstruction and 3DTV. However, the resolution of captured depth image is much lower than that of its corresponding color image, which affects its application performance. In this paper, we propose a novel depth map super-resolution (SR) method by taking view synthesis quality into account. The proposed approach mainly includes two technical contributions. First, since the captured low-resolution (LR) depth map may be corrupted by noise and occlusion, we propose a credibility based multi-view depth maps fusion strategy, which considers the view synthesis quality and interview correlation, to refine the LR depth map. Second, we propose a view synthesis quality based trilateral depth-map up-sampling method, which considers depth smoothness, texture similarity and view synthesis quality in the up-sampling filter. Experimental results demonstrate that the proposed method outperforms state-of-the-art depth SR methods for both super-resolved depth maps and synthesized views. Furthermore, the proposed method is robust to noise and achieves promising results under noise-corruption conditions.


Cimetidine psychotoxicity without significant medical illness: case report.
Previous reports have described cimetidine psychotoxicity as predominantly an organic brain syndrome in older, severely ill patients. This paper reports a cimetidine-induced mental state change in a middle-aged man with a relatively uncomplicated medical history. Since toxic effects of cimetidine are likely to occur within 1 to 2 days of starting the medication, close observation during this time period, and prompt recognition of psychotoxicity, can prevent disruptive side effects.


What investigations are needed to optimally monitor for malignancies in SLE?
The overall cancer incidence risk in systemic lupus erythematosus (SLE) is approximately 15%-20% more than in the general population. Nevertheless, to date, the optimal malignancy screening measures in SLE remain undefined. Our objective is to determine what investigations are needed to optimally monitor for malignancies in SLE in order to inform upcoming Canadian Rheumatology Association recommendations. We conducted a systematic search looking at three scientific sources, Embase, Medline and Cochrane, in an attempt to identify cancer screening recommendations for patients with SLE. We used a filter for observational studies and included articles published in 2000 and onward. The initial search strategy led to 986 records. After removal of duplicates and articles unrelated to SLE, we were left with 497 titles. From those, 79 research articles on cancer incidence in SLE were isolated and reviewed. Of the 79 original research papers, 25 offered screening recommendations, 14 suggested additional cancer screening whereas 11 studies simply promoted adherence to general population screening measures. The suggestions for more rigorous screening included recommending human papilloma virus testing in addition to routine cervical screening, and/or that cervical screening should be performed annually and/or suggested urine cancer screening in SLE patients with a history of cyclophosphamide exposure. We found no original research studies directly comparing cancer screening strategies in SLE. Generally, authors recommend adherence to general population screening measures, particularly cervical screening. This, possibly with adding targeted screening in special cases (e.g. annual urine cytology in patients with prior cyclophosphamide exposure, and considering existing lung cancer screening guidelines for past heavy smokers), may be a reasonable approach for cancer screening in SLE.


Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.
Cerebral malaria (CM) is a severe neurological complication caused by Plasmodium falciparum parasites; it is characterized by the sequestration of infected red blood cells within the cerebral microvasculature. New findings, combined with a better understanding of the central nervous system (CNS) barriers, have provided greater insight into the players and events involved in CM, including site-specific T cell responses in the human brain. Here, we review the updated roles of innate and adaptive immune responses in CM, with a focus on the role of the perivascular macrophage-endothelium unit in antigen presentation, in the vascular and perivascular compartments. We suggest that these events may be pivotal in the development of CM.


Born this way: Sexual orientation beliefs and their correlates in lesbian and bisexual women.
In this study, we examined how beliefs about the nature and origin of sexual orientation were associated with sexual identity outcomes, namely internalized sexual stigma and sexual orientation uncertainty, and in turn, psychological well-being in sexual minority women. A community sample of 393 lesbian and 205 bisexual women were recruited for a cross-sectional online survey. Using multigroup structural equation modeling, we examined whether believing sexual orientation to be inborn/immutable (i.e., natural) and/or as existing in discrete categories (i.e., discrete) was indirectly associated with psychological well-being via internalized stigma and sexual orientation uncertainty and whether some of these relationships were moderated by nonprototypical attractions (nonexclusive same-sex attractions in lesbian women and straight- or lesbian-leaning attractions in bisexual women) and age. Overall, similar patterns of direct effects were observed in lesbian and bisexual women. In both groups, naturalness beliefs were associated with lower internalized-stigma, whereas discreteness beliefs were associated with greater internalized stigma. In bisexual women, nonprototypical sexual attraction patterns moderated the relationship between discreteness beliefs and sexual orientation uncertainty. Younger age was associated with increased sexual orientation uncertainty in both lesbian and bisexual women. Specific to lesbian women, nonprototypical attraction predicted less endorsement of immutability and binary/discrete beliefs about sexual orientation, and unexpectedly, greater internalized stigma. The present study identifies potential implications of common lay theories of sexual orientation for lesbian versus bisexual women. (PsycINFO Database Record


Optic nerve circulation and ocular pressure.
Rapid, short-lasting elevation of ocular pressure level produces simultaneous reduction in blood-flow rate in the distal 6 mm. of the extraocular portion of the optic nerve of the rhesus monkey as monitored by the heated thermocouple technique. The magnitude of this reduction was very small until intraocular pressure (IOP) exceeded 50 mm. Hg following which markedly and progressively greater reduction in blood-flow rate occurred at higher IOP levels; maximum reduction was reached at IOP of 105 mm. Hg. The magnitude of reduction in blood-flow rate for each ocular pressure level was significantly greater when systemic arterial pressure was reduced. These effects were monitored 2 to 4 mm. behind the globe and became reduced at a more proximal location, disappearing at locations further than 6 mm. from the globe. The results suggested a reduction in nutrient blood flow to the optic nerve at the monitored site with elevation of IOP.


Lactococcus lactis gene yjgB encodes a gamma-D-glutaminyl-L-lysyl-endopeptidase which hydrolyzes peptidoglycan.
YjgB is one of five peptidoglycan hydrolases previously identified in Lactococcus lactis. Analysis of its amino acid sequence revealed that YjgB contains an NlpC/P60 domain, whereas no specific cell wall binding domain or motif could be identified. The NlpC/P60 family is characterized by three conserved residues, a cysteine, a histidine, and a polar residue. In agreement with the presence of a Cys residue in the catalytic site of YjgB, its enzymatic activity was enhanced in the presence of dithiothreitol. Peptidoglycan-hydrolyzing activity of YjgB was detected in growing cells of an L. lactis strain overexpressing YjgB, as revealed by the presence of disaccharide (DS)-dipeptide in the muropeptide composition of the overexpressing strain. YjgB hydrolyzes the peptide chains of L. lactis muropeptides between gamma-D-Gln and L-Lys residues. Its hydrolytic activity was detected on DSs with tetra- and pentapeptide chains, whereas hydrolytic activity was very low on DS-tripeptides. Thus, we demonstrated that YjgB is an endopeptidase which cleaves gamma-D-Gln-L-Lys bonds in peptide chains of L. lactis peptidoglycan.


[Evaluation of the Oran university hospital information system].
Oran university hospital has been operating since 2010. It is a public institution that must assess the resources required to achieve institutional goals integrated into the strategic objectives defined in the hospital development project. Implementation of this project could be supported, among other things, by a strong and efficient hospital information system. Three investigations were conducted: 1- evaluation of the hospital information system, 2- assessment of the quality of the hospital discharge summary reports, 3- assessment of the quality of medical records. The six components of the hospital information system (resources, indicators, sources, management, quality and dissemination and use of data) were clearly present but not satisfactory with a score ranging from 25 to 50% of the total score. The scores by component were as follows: 36% for resources, 37% for indicators, 42% for patient records, 19% for data management and 27% for the dissemination of information. The overall completeness of medical records was 85.2%. Completeness by group of variables gave the following results: 66% for medical information, 54% for the patient's stay and 38% for information relating to the patient's discharge. Hospital discharge summary reports were available in 59.8% of cases, but were blank in 4% of cases. The critical variable, the principal diagnosis was found in 51% of cases. The correct principal diagnosis rate was 33.3%. The deficiencies observed for content and data management raise real questions concerning data management at Oran university hospital as part of a real managerial approach.


Altered gene expression in melanocytes exposed to 4-tertiary butyl phenol (4-TBP): upregulation of the A2b adenosine receptor 1.
Exposure to phenolic agents contributes to the development of occupational vitiligo. Proposed as a causative factor for leukoderma in vivo, the para-substituted phenol 4-tertiary butyl phenol was chosen to investigate early cellular events responsible for selective disappearance of melanocytes from the epidermis of individuals sensitive to such agents. To this end, differential display of melanocyte mRNA isolated from three separate cultures was performed following a 12 h exposure of cells to 250 microM 4-tertiary butyl phenol or to vehicle alone. Fragments of cDNA representing differentially expressed messages were cloned and subsequently confirmed by reverse dot blotting. Alignment analysis revealed that the L30 ribosomal protein was upregulated by the treatment, potentially reflecting altered levels of protein synthesis in response to stress. In addition, a gene sequence upregulated following exposure to 4-tertiary butyl phenol was identified as the A2b receptor (a P1 receptor for adenosine). Differential expression of this gene was confirmed in an RNase protection assay. By reverse transcription-polymerase chain reaction, the gene was shown to be expressed in keratinocytes and fibroblasts as well. Flow cytometry confirmed differential expression in melanocytes and fibroblasts, but not in keratinocytes. Interestingly, it has been reported that P1 purinoceptor stimulation can induce apoptosis. This is in concordance with results reported elsewhere demonstrating induction of apoptosis by 4-tertiary butyl phenol in human melanocytes, as well as with morphologic changes observed in this study in cells exposed to 250 microM 4-tertiary butyl phenol for 72 h. In conclusion, differential display is useful to establish melanocyte components involved in the cellular response to phenolic agents.


How intermediate tax sanctions may be applied to IDSs.
Recently issued proposed regulations describing how the IRS intends to enforce the intermediate tax sanctions statute of the Internal Revenue Code have important ramifications for integrated delivery systems (IDSs). The regulations' interpretation of who within an IDS may be subject to excise taxes under the statute is broad, basing an individual's risk of being taxed on his or her degree of influence over a given entity within the organization, rather than over the organization as a whole. To protect individuals within an IDS from exposure to intermediate tax sanctions, the organization should understand who is likely to be at risk and take steps to ensure that all transactions with such persons are in compliance with the conditions set forth in the proposed regulations.


Intimate Partner Violence: Using Standardized Patients to Improve Trauma-Informed Care in the era of the Covid-19 Pandemic.
This article was migrated. The article was marked as recommended. Intimate partner violence (IPV) is a global public health problem that has been exacerbated by the social isolation measures currently in place in countries around the world. The authors appreciate the importance of teaching medical students the skill sets to cope with the recognition and diagnosis and medical management of IPV. This is because physicians are most often the first point of contact for victims of IPV. It is also essential to ensure medical students become self-aware of the emotional triggers which may be associated with caring for victims of IPV. This opinion piece explains how medical educators can make a difference in training future physicians in caring for victims of IPV. With the current COVID-19 pandemic bringing the issue of IPV sharply into focus, this paper outlines why medical educators should ensure that medical students are equipped to deal with the societal consequences emanating from the COVID-19 pandemic which will reverberate into the future. Therefore, there is no more time to waste. We are facing a critical juncture, with the current cohort of medical students and physicians exposed to the disproportionately high levels of personal, professional, and emotional trauma that have resulted from the COVID-19 pandemic. Training is imperative; it is of paramount importance for our future medical professionals to be self-aware of their emotional triggers.


A V1-like receptor mediates vasopressin-induced flank marking behavior in hamster hypothalamus.
A vasopressin-sensitive mechanism within the medial preoptic area-anterior hypothalamus (MPOA-AH) appears to be essential for expression of a complex behavior involved in olfactory communication in Golden hamsters called flank marking. The present study investigated whether the induction of flank marking by arginine-vasopressin (AVP) within the MPOA-AH is mediated by a receptor that is more similar to the vasopressor (V1) or the antidiurectic (V2) AVP receptor. Adult male hamsters were anesthetized and implanted with a 26 gauge guide cannula stereotaxically aimed at the MPOA-AH and then microinjected with analogs of vasopressin, oxytocin, and selective V1 and V2 antagonists. Hamsters were tested for flank-marking behavior during a 5 or 10 min observation period following the injection of peptide in a vehicle of 100 nl of saline. None of the 15 analogs of AVP and oxytocin produced more flank marking than the 50.8 +/- 16.2 and 76.8 +/- 4.4 (mean +/- SEM; n = 4) flank marks observed following injection of AVP at the 1 or 10 ng dose, respectively. The number of flank marks produced by each analog was found to be highly related to the pressor activity of that analog at both the 1 ng (rho = +0.74, p less than 0.01) and 10 ng (rho = +0.82, p less than 0.01) doses. In contrast, no statistically reliable relationship between flank marking and the antidiuretic activity of these analogs was found at either dose (1 ng: rho = +0.07, p greater than 0.05; 10 ng: rho = +0.10, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Pseudomembranous colitis: pathogenesis, prevention, treatment].
The article reviews a pathogenesis of Pseudomembranous colitis. Questions of prevention and treatment of Clostridium difficile--associated diarrhea are shown by the Evidence-based medicine. There is an accent on the rational prescription of antibiotics.


Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C.
Recently, several cases of symptomatic, sometimes fatal bradycardia during the first days of direct-acting antiviral (DAA) (eg, sofosbuvir [SOF]) administration have been reported. We analyzed in detail electrocardiographic (ECG) changes during SOF- or non-SOF-based chronic hepatitis C (CHC) treatment, specifically focusing on bradyarrhythmias. All 39 consecutive patients treated at our center with any interferon-free regimen between June and December 2015 were included in this study (26 SOF-based therapy vs 13 no-SOF interferon-free regimens). ECG tracings were obtained from all patients the first day of treatment and after 7, 14, and 28 days. ECG parameters (P-wave, QRS, QT interval, JT interval, Tapex -Tend interval duration) were compared between the 2 groups at baseline and at the 3 different time points during antiviral therapy. There were no cases of symptomatic bradycardia/syncope. In the SOF group, QTc duration rose after 1 week (from 424.3 to 431.2 milliseconds; P = .013) and returned to baseline during therapy. QT dispersion dropped since week 1 (from 85.6 to 67.2 milliseconds) and remained significantly reduced until the end of the observation period (72.9 msec) (P = .003). JT dispersion reduced up to week 2 (P = .010) and returned to baseline at week 4; in the no-SOF group, QRS dispersion transiently reduced (from 41 to 34.5 milliseconds, day 7). No other significant changes were observed in the remaining parameters. In CHC patients treated with SOF and other DAAs, ECG parameter changes were mild and/or transient and did not translate into clinically significant electrophysiological effects in the absence of amiodarone coadministration.


Seizure-related autonomic changes in children.
Although sudden unexpected death in epilepsy is encountered less frequently in children versus adults, it is still an important direct epilepsy-related cause of death in this population. Just as in adults, the pathophysiology of sudden unexpected death in epilepsy in children is believed to involve seizure-related autonomic dysfunction. Seizures that develop during the pediatric period can be marked by some of the most dramatic alterations in autonomic functions seen at any age. This article reviews such seizure-related autonomic changes, including ictal nausea/emesis, hypersalivation, hypoxemia, apnea, tachycardia, bradycardia, cardiac repolarization anomalies, reduced heart rate variability, and postictal generalized EEG suppression. Understanding age-related changes in the autonomic effects of seizures and how they relate to risk of sudden death may help us to one day better elucidate the pathophysiology of sudden unexpected death in epilepsy. Given the high rate of sudden unexpected death in epilepsy in certain pediatric populations (such as those with Dravet syndrome), this knowledge is desperately needed.


Early-life microbiota transplantation affects behavioural responses, serotonin and immune characteristics in chicken lines divergently selected on feather pecking.
Gut microbiota influences host behaviour and physiology, such as anxiety, stress, serotonergic and immune systems. These behavioural and physiological characteristics are related to feather pecking (FP), a damaging behaviour in chickens that reduces animal welfare and productivity. Moreover, high FP (HFP) and low FP (LFP) lines differed in microbiota composition. However, it is unknown whether microbiota can influence the development of FP. For the first time, we identified the effects of microbiota transplantation on FP, and behavioural and physiological characteristics related to FP. HFP and LFP chicks received sterile saline (control), HFP or LFP microbiota transplantation during the first two weeks post-hatch. Microbiota transplantation influenced behavioural responses of the HFP line during treatment and of the LFP line after treatment. In both lines, homologous microbiota transplantation (i.e., receiving microbiota from their line) resulted in more active behavioural responses. Furthermore, microbiota transplantation influenced immune characteristics (natural antibodies) in both lines and peripheral serotonin in the LFP line. However, limited effects on microbiota composition, stress response (corticosterone) and FP were noted. Thus, early-life microbiota transplantation had immediate and long-term effects on behavioural responses and long-term effects on immune characteristics and peripheral serotonin; however, the effects were dependent on host genotype. Since early-life microbiota transplantation influenced behavioural and physiological characteristics that are related to FP, it could thus influence the development of FP later in life.


Graphene-Oxide-Assisted Synthesis of GaN Nanosheets as a New Anode Material for Lithium-Ion Battery.
As the most-studied III-nitride, theoretical researches have predicted the presence of gallium nitride (GaN) nanosheets (NSs). Herein, a facile synthesis approach is reported to prepare GaN NSs using graphene oxide (GO) as sacrificial template. As a new anode material of Li-ion battery (LIBs), GaN NSs anodes deliver the reversible discharge capacity above 600 mA h g-1 at 1.0 A g-1 after 1000 cycles, and excellent rate performance at current rates from 0.1 to 10 A g-1. These results not only extend the family of 2D materials but also facilitate their use in energy storage and other applications.


Small-volume d-β-hydroxybutyrate solution infusion increases survivability of lethal hemorrhagic shock in rats.
A small-volume therapeutic approach based on the biochemistry of hibernating mammals was evaluated to test the hypothesis that passive hypothermia and systemic administration of d-β-hydroxybutyrate (d-BHB) plus melatonin will increase survival of animals subjected to hemorrhagic shock ([HS] 60% blood loss). Anesthetized Sprague-Dawley male rats (320 ± 23 g) underwent controlled loss of 60% blood volume. Rats were instrumented to measure mean arterial pressure, body temperature (Tb), and heart rate. A passive decrease in rat Tb in response to HS significantly increased survival over animals maintained at 37°C (n = 5-6). Infusion of 4 M d-BHB, at a volume of only 5.5% of the total blood removed, significantly prolonged survival to a mean of 3 h compared with 90 min using equal osmolar 4 M NaCl (n = 6). In experiments where the shed blood was returned after 1 h of 60% blood loss, 4% fluid replacement with 4 M d-BHB plus 43 mM melatonin significantly prolonged survival up to 10 days after blood return compared with 4 M NaCl plus 43 mM melatonin and other control solutions (n = 10). We conclude that a slow decrease in animal Tb resulting from 60% blood loss, combined with infusion of 4 M d-BHB plus 43 mM melatonin, was beneficial for long-term survival after return of shed blood. This HS therapy is designed as a portable low-volume solution for further evaluation in a large-animal model and is ultimately intended for use in HS patients by first responders.


Toward transferable interatomic van der Waals interactions without electrons: the role of multipole electrostatics and many-body dispersion.
We estimate polarizabilities of atoms in molecules without electron density, using a Voronoi tesselation approach instead of conventional density partitioning schemes. The resulting atomic dispersion coefficients are calculated, as well as many-body dispersion effects on intermolecular potential energies. We also estimate contributions from multipole electrostatics and compare them to dispersion. We assess the performance of the resulting intermolecular interaction model from dispersion and electrostatics for more than 1300 neutral and charged, small organic molecular dimers. Applications to water clusters, the benzene crystal, the anti-cancer drug ellipticine-intercalated between two Watson-Crick DNA base pairs, as well as six macro-molecular host-guest complexes highlight the potential of this method and help to identify points of future improvement. The mean absolute error made by the combination of static electrostatics with many-body dispersion reduces at larger distances, while it plateaus for two-body dispersion, in conflict with the common assumption that the simple 1/R(6) correction will yield proper dissociative tails. Overall, the method achieves an accuracy well within conventional molecular force fields while exhibiting a simple parametrization protocol.


Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline.
High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports. With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ("agree moderately") or 6 ("agree strongly"). Reporting elements that ≥70% of panelists rated as "agree moderately" or "agree strongly" were considered to have achieved consensus. Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report. It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.


Whole mitochondrial and chloroplast genome sequencing of Tunisian date palm cultivars: diversity and evolutionary relationships.
Date palm (Phoenix dactylifera L.) is the most widespread crop in arid and semi-arid regions and has great traditional and socioeconomic importance, with its fruit well-known for its high nutritional and health value. However, the genetic variation of date palm cultivars is often neglected. The advent of high-throughput sequencing has made possible the resequencing of whole organelle (mitochondria and chloroplast) genomes to explore the genetic diversity and phylogenetic relationships of cultivated plants with unprecedented detail. Whole organelle genomes of 171 Tunisian accessions (135 females and 36 males) were sequenced. Targeted bioinformatics pipelines were used to identify date palm haplotypes and genome variants, aiming to provide variant annotation and investigate patterns of evolutionary relationship. Our results revealed the existence of unique haplotypes, identified by 45 chloroplastic and 156 mitochondrial SNPs. Estimation of the effect of these SNPs on genes functions was predicted in silico. The results of this study have important implications, in the light of ongoing environmental changes, for the conservation and sustainable use of the genetic resources of date palm cultivars in Tunisia, where monoculture threatens biodiversity leading to genetic erosion. These data will be useful for breeding and genetic improvement programs of the date palm through selective cross-breeding.


Periconal arterial anastomotic circle and posterior lumbosacral watershed zone of the spinal cord.
The existence of spinal cord watershed territories was suggested in the 1950s. Segmental infarcts within the junctional territories of adjacent radiculomedullary contributors and isolated spinal gray matter ischemia constitute two well-recognized types of watershed injury. This report describes the existence of another watershed territory related to the particular configuration of the spinal vasculature in the region of the conus medullaris. The anatomical bases underlying the concept of a posterior lumbosacral watershed zone are demonstrated with angiographic images obtained in a 16-year-old child. The clinical importance of this watershed zone is illustrated with MRI and angiographic data of three patients with a conus medullaris infarction. In all three cases of spinal ischemia an intersegmental artery providing a significant radiculomedullary contribution for the lower cord was compromised by a compressive mechanism responsible for decreased spinal cord perfusion (diaphragmatic crus syndrome in two cases, disk herniation in one). The ischemic injury, located at the junction of the anterior and posterior spinal artery territories along the dorsal aspect of the conus medullaris, was consistent with a watershed mechanism. This zone is at risk because of the caudocranial direction of flow within the most caudal segment of the posterior spinal arterial network which, from a functional standpoint, depends on the anterior spinal artery. The posterior thoracolumbar watershed zone of the spinal cord represents an area at increased risk of ischemic injury, particularly in the context of partial flow impairment related to arterial compression mechanisms.


Morphogenetic effects of light and guanine derivatives on the fruiting myxobacterium Stigmatella aurantiaca.
When low cell densities of the myxobacterium Stigmatella aurantiaca were starved on an inorganic salts and agar medium, cell aggregation and fruiting body formation showed a striking dependency upon the presence of light. This dependency was not manifested when sufficient amounts of guanosine or guanine nucleotides were added to the medium. Light interacted cooperatively with suboptimal concentrations of guanine compounds to promote development. None of the other purine or pyrimidine derivatives, with the exception of adenine, stimulated development. However, aggregates that formed in the presence of adenine did not mature into fruiting bodies and instead disaggregated.


Ω3 Supplementation and intermittent hypobaric hypoxia induce cardioprotection enhancing antioxidant mechanisms in adult rats.
Intermittent hypobaric hypoxia (IH) is linked with oxidative stress, impairing cardiac function. However, early IH also activate cardio-protective mechanisms. Omega 3 fatty acids (Ω3) induce cardioprotection by reducing infarct size and reinforcing antioxidant defenses. The aim of this work was to determine the combined effects of IH and Ω3 on cardiac function; oxidative balance and inflammatory state. Twenty-eight rats were randomly divided into four groups: normobaric normoxia (N); N + Ω3 (0.3 g·kg-1·day-1); IH; and IH + Ω3. IH was induced by 4 intercalate periods of hypoxia (4 days)-normoxia (4 days) in a hypobaric chamber during 32 days. At the end of the exposure, hearts were mounted in a Langendorff system and subjected to 30 min of ischemia followed by 120 min of reperfusion. In addition, we determined HIF-1α and ATP levels, as well as oxidative stress by malondialdehyde and nitrotyrosine quantification. Further, the expression of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase was determined. NF-kappaB and myeloperoxidase levels were assessed in the hearts. Relative to N hearts, IH improved left ventricular function (Left ventricular developed pressure: N; 21.8 ± 3.4 vs. IH; 42.8 ± 7.1 mmHg; p < 0.05); reduced oxidative stress (Malondialdehyde: N; 14.4 ± 1.8 vs. IH; 7.3 ± 2.1 μmol/mg prot.; p < 0.05); and increased antioxidant enzymes expression. Supplementation with Ω3 induces similar responses as IH group. Our findings suggest that both, IH and Ω3 in an independent manner, induce functional improvement by antioxidant and anti-inflammatory mechanisms, establishing cardio-protection.


Maternal hemodynamics: a method to classify hypertensive disorders of pregnancy.
The classification of hypertensive disorders of pregnancy is based on the time at the onset of hypertension, proteinuria, and other associated complications. Maternal hemodynamic interrogation in hypertensive disorders of pregnancy considers not only the peripheral blood pressure but also the entire cardiovascular system, and it might help to classify the different clinical phenotypes of this syndrome. This study aimed to examine cardiovascular parameters in a cohort of patients affected by hypertensive disorders of pregnancy according to the clinical phenotypes that prioritize fetoplacental characteristics and not the time at onset of hypertensive disorders of pregnancy. At the fetal-maternal medicine unit of Ziekenhuis Oost-Limburg (Genk, Belgium), maternal cardiovascular parameters were obtained through impedance cardiography using a noninvasive continuous cardiac output monitor with the patients placed in a standing position. The patients were classified as pregnant women with hypertensive disorders of pregnancy who delivered appropriate- and small-for-gestational-age fetuses. Normotensive pregnant women with an appropriate-for-gestational-age fetus at delivery were enrolled as the control group. The possible impact of obesity (body mass index ≥30 kg/m2) on maternal hemodynamics was reassessed in the same groups. Maternal age, parity, body mass index, and blood pressure were not significantly different between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and hypertensive disorders of pregnancy/small-for-gestational-age groups. The mean uterine artery pulsatility index was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group. The cardiac output and cardiac index were significantly lower in the hypertensive disorders of pregnancy/small-for-gestational-age group (cardiac output 6.5 L/min, cardiac index 3.6) than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group (cardiac output 7.6 L/min, cardiac index 3.9) but not between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and control groups (cardiac output 7.6 L/min, cardiac index 4.0). Total vascular resistance was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group and the control group. All women with hypertensive disorders of pregnancy showed signs of central arterial dysfunction. The cardiovascular parameters were not influenced by gestational age at the onset of hypertensive disorders of pregnancy, and no difference was observed between the women with appropriate-for-gestational-age fetuses affected by preeclampsia or by gestational hypertension with appropriate-for-gestational-age fetuses. Women in the obese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and obese/hypertensive disorders of pregnancy/small-for-gestational-age groups showed a significant increase in cardiac output, as well as significant changes in other parameters, compared with the nonobese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and nonobese/hypertensive disorders of pregnancy/small-for-gestational-age groups. Significantly low cardiac output and high total vascular resistance characterized the women with hypertensive disorders of pregnancy associated with small for gestational age due to placental insufficiency, independent of the gestational age at the onset of hypertension. The cardiovascular parameters were not significantly different in the women with appropriate-for-gestational-age or small-for-gestational-age fetuses affected by preeclampsia or gestational hypertension. These findings support the view that maternal hemodynamics may be a candidate diagnostic tool to identify hypertensive disorders in pregnancies associated with small-for-gestational-age fetuses. This additional tool matches other reported evidence provided by uterine Doppler velocimetry, low vascular growth factors in the first trimester, and placental pathology. Obesity is associated with a significantly higher cardiac output and outweighs other determinants of hemodynamics in pregnancy; therefore, in future studies on hypertensive disorders, obesity should be studied as an additional disease and not simply as a demographic characteristic.


Review on dog rabies vaccination coverage in Africa: a question of dog accessibility or cost recovery?
Rabies still poses a significant human health problem throughout most of Africa, where the majority of the human cases results from dog bites. Mass dog vaccination is considered to be the most effective method to prevent rabies in humans. Our objective was to systematically review research articles on dog rabies parenteral vaccination coverage in Africa in relation to dog accessibility and vaccination cost recovery arrangement (i.e.free of charge or owner charged). A systematic literature search was made in the databases of CAB abstracts (EBSCOhost and OvidSP), Scopus, Web of Science, PubMed, Medline (EBSCOhost and OvidSP) and AJOL (African Journal Online) for peer reviewed articles on 1) rabies control, 2) dog rabies vaccination coverage and 3) dog demography in Africa. Identified articles were subsequently screened and selected using predefined selection criteria like year of publication (viz. ≥ 1990), type of study (cross sectional), objective(s) of the study (i.e. vaccination coverage rates, dog demographics and financial arrangements of vaccination costs), language of publication (English) and geographical focus (Africa). The selection process resulted in sixteen peer reviewed articles which were used to review dog demography and dog ownership status, and dog rabies vaccination coverage throughout Africa. The main review findings indicate that 1) the majority (up to 98.1%) of dogs in African countries are owned (and as such accessible), 2) puppies younger than 3 months of age constitute a considerable proportion (up to 30%) of the dog population and 3) male dogs are dominating in numbers (up to 3.6 times the female dog population). Dog rabies parenteral vaccination coverage was compared between "free of charge" and "owner charged" vaccination schemes by the technique of Meta-analysis. Results indicate that the rabies vaccination coverage following a free of charge vaccination scheme (68%) is closer to the World Health Organization recommended coverage rate (70%) than the achieved coverage rate in owner-charged dog rabies vaccination schemes (18%). Most dogs in Africa are owned and accessible for parenteral vaccination against rabies if the campaign is performed "free of charge".


Sleep/wake regularity and cognition in college students using antidepressants.
The current project examined sleep, sleep/wake regularity, and cognition in college students diagnosed with depression and using serotonergic antidepressants and in those without a depression diagnosis. Forty participants either using antidepressants (n = 20, 24.75 ± 6.82 years) or without a depression diagnosis (n = 20, 21.70 ± 2.74 years) wore actigraphs for two consecutive weeks (14 days). Cognitive tasks were completed on day 1 (along with demographic surveys) and day 14. Effect sizes indicated that compared to non-clinically depressed peers, participants using antidepressants exhibited slightly greater wake after sleep onset (d = 0.36) and lower sleep efficiency (d = 0.40); however, these differences were likely not noticed by the sleeper. No sleep regularity or cognitive differences were present between groups. Within the antidepressant group, higher dosage predicted greater time in bed (R2 = 0.77), but less total sleep time (R2 = 0.86). The time of day that participants took their antidepressant exhibited differential effects on certain cognitive parameters, such as procedural reaction time and spatial processing, and interactions with years of antidepressant use were found. Self-reported wake episodes also predicted better reaction time and inhibition in the antidepressant group. This study is the first to demonstrate that sleep/wake regularity is comparable between people using antidepressants and non-clinically depressed human samples. For individuals using antidepressants, years of use, dosage, and time of day of use have predictive qualities for reaction times, spatial processing, and inhibition.


A qualitative study to explore views of patients', carers' and mental health professionals' to inform cultural adaptation of CBT for psychosis (CBTp) in China.
The evidence for effectiveness of Cognitive Behaviour Therapy (CBT) is robust and the national organizations in the United Kingdom and the United States recommend its use. It is not utilized to its full potential in low and middle-income countries. Adaptation of CBT treatment to the target culture may facilitate its uptake. This study explored views of patients with schizophrenia, their caregivers, and mental health professionals for the purpose of cultural adaptation of CBT. The project was conducted in a teaching hospital in China. Systematic content and question analysis were the techniques we used to analyse the data generated in a series of qualitative interviews (N 45) in China. After identification of emerging themes and categories we compared and contrasted the themes across different interviews recursively. Triangulation of themes and concepts was undertaken to compare further and contrast the data from the different participating groups. This work highlighted the barriers in therapy as well as opportunities for use of CBT in that environment. Patients and their carers in China use a bio-psycho-spiritual-social model of illness. CBT is not commonly used to help those with schizophrenia in China. This study will facilitate the therapists using CBT for people with psychosis in China. These results require to be tested in clinical trials.


Prospective study of snoring and risk of hypertension in women.
Whether snoring increases the risk of hypertension remains unclear. The authors examined the association between snoring and risk of hypertension in a cohort of 73,231 US female nurses aged 40-65 years and without diagnosed cardiovascular disease or cancer in 1986. Blood pressure levels and physician-diagnosed hypertension were self-reported through validated questionnaires. During 8 years of follow-up, 7,622 incident cases of physician-diagnosed hypertension were reported. Older age, smoking, body mass index, waist circumference, waist-hip ratio, weight gain, less physical activity, and sleeping on the back were directly associated with regular snoring. After adjustment for age, body mass index, waist circumference, and other covariates, snoring was associated with a significantly higher prevalence of hypertension at baseline (odds ratio = 1.22, 95% confidence interval (CI): 1.16, 1.27 for occasional snoring and odds ratio = 1.43, 95% CI: 1.33, 1.5 for regular snoring). In prospective analyses using incident cases of hypertension as the outcome, the multivariate relative risks of hypertension were 1.29 (95% CI: 1.22, 1.37) for occasional snoring and 1.55 (95% CI: 1.42, 1.70) for regular snoring. In addition, snoring was associated with significantly higher systolic and diastolic blood pressure levels. These data suggest that snoring may increase risk of hypertension in women, independent of age, body mass index, waist circumference, and other lifestyle factors.


Integrating air pollution modelling with scenario testing in road transport planning: the TRAEMS approach.
Transport add-on environmental modelling system (TRAEMS) is a GIS-based environmental modelling system designed to evaluate the environmental consequences of road traffic in urban areas. Its development has been underpinned by the premises that the evaluation of road traffic impacts is best undertaken during the early planning stages of road networks, and that this can utilise much of the data generated by the transport planners themselves as they apply their travel demand models as to planning of road networks. The system integrates information about traffic-usually from travel-forecasting models-with information about land use, to provide the input data to a range of commonly used models that estimate pollution from a road traffic system, and the energy consumption of that system. TRAEMS facilitates this integration and allows land use, transport and environmental planners to have rapid feedback on the environmental effects of road transport network scenarios that are being developed and tested. Its purpose is to aid in the selection of environmentally-preferred road networks and to highlight where management of pollution levels on future road networks will be required. TRAEMS has a modular structure. This paper describes the main features of the air pollution and fuel consumption modules of the system and illustrates the system's utility through case studies at both metropolitan-wide- and local-area scales.


The closed-edge structure of graphite and the effect of electrostatic charging.
The properties of graphite, and of few-layer graphene, can be strongly influenced by the edge structure of the graphene planes, but there is still much that we do not understand about the geometry and stability of these edges. We present an experimental and theoretical study of the closed edges of graphite crystals, and of the effect of an electric field on their structure. High-resolution transmission electron microscopy is used to image the edge structure of fresh graphite and of graphite that has been exposed to an electric field, which experiences a separation of the graphene layers. Computer simulations based on density functional theory are used to rationalise and quantify the preference for the formation of multiple concentric loops at the edges. A model is also presented to explain how the application of an electric field leads to the separation of the folded edges.


Apparent Diffusion Coefficient Predicts Pathology Complete Response of Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy.
To evaluate the predictive value of the apparent diffusion coefficient (ADC) for pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer. A total of 265 patients with rectal adenocarcinoma, whole Diffusion-Weighted MRI (DWI-MRI) images, clinically stage II to III (cT3-4 and/or cN+) and treated with NCRT followed by TME were screened. Fifty patients with pCR and another 50 patients without pCR with similar clinical charcacters and treatment regimens were selected for statistical analysis. All the patients' pre-CRT and post-CRT average ADC values were calculated from the coefficient maps created by DWI-MRI and recorded independently. The difference in the ADC values between the pCR and non-pCR was analyzed by the Mann-Whitney U test. The cut-off ADC value of the receiver operating characteristic (ROC) curve with pCR was then established. The mean pre- and post-ADC values in all patients, and in pCR patients and non-pCR patients were 0.879±0.06 and 1.383±0.11, 0.859±0.04 and 1.440±0.10, 0.899±0.07 and 1.325±0.09 (×10(-3) mm(2)/s), respectively. The difference between the pre- and post-ADC values in all patients, pCR patients, and non-pCR patients were considered to be statistically significant. The pre-ADC value was significantly lower in the pCR patients than in the non-pCR patients (p = 0.003), whereas the post-ADC values were significantly higher in the pCR patients than in the non-pCR patients. The percentage increase of the ADC value (ΔADC%) in the pCR and non-pCR patients were 68% and 48% respectively (p<0.001). The ROC curves of the cut-off value of the pre-CRT patient ADC value was 0.866×10(-3) mm(2)/s. The AUC, sensitivity, specificity, PPV, NPV, and accuracy of diagnosing pCR were 0.670 (95% CI 0.563-0.777), 0.600, 0.640, 60%, 60%, and 60%, respectively. The cut-off value of ΔADC% was 58%. The corresponding AUC, sensitivity, specificity, PPV, NPV, and accuracy of diagnosing pCR were 0.856 (95% CI 0.783-0.930), 0.800, 0.760, 76.9%, 79.2%, and 78%, respectively. DWI-MRI technology can be efficient for predicting pCR for LARC after NCRT. Although the mean pre-CRT ADC value and the ΔADC% are moderate predictors for pCR, the latter would be more accurate.


Temporal and region-specific requirements of αCaMKII in spatial and contextual learning.
The α isoform of the calcium/calmodulin-dependent protein kinase II (αCaMKII) has been implicated extensively in molecular and cellular mechanisms underlying spatial and contextual learning in a wide variety of species. Germline deletion of Camk2a leads to severe deficits in spatial and contextual learning in mice. However, the temporal and region-specific requirements for αCaMKII have remained largely unexplored. Here, we generated conditional Camk2a mutants to examine the influence of spatially restricted and temporally controlled expression of αCaMKII. Forebrain-specific deletion of the Camk2a gene resulted in severe deficits in water maze and contextual fear learning, whereas mice with deletion restricted to the cerebellum learned normally. Furthermore, we found that temporally controlled deletion of the Camk2a gene in adult mice is as detrimental as germline deletion for learning and synaptic plasticity. Together, we confirm the requirement for αCaMKII in the forebrain, but not the cerebellum, in spatial and contextual learning. Moreover, we highlight the absolute requirement for intact αCaMKII expression at the time of learning.


Bioinformatic analysis of microarray data reveals several key genes related to heart failure.
Heart failure is a major public health problem worldwide. However, the molecular mechanism is still unclear. This study aims to discover differentially expressed genes (DEGs) between non-ischemic or ischemic heart failure samples and healthy control, which may be used for diagnosis and treatment of heart failure. Gene expression profile GSE9128 was downloaded from Gene Expression Omnibus, including 3 normal samples, 4 non-ischemic heart failure samples and 4 ischemic samples. Data processing and differential analysis were carried out with packages of R. Cluster analysis was also performed for all the samples to globally observe the difference among the three groups of samples. Interactors of the DEGs were retrieved with Osprey and then networks were constructed. The overlapping part of the network was selected out using Cytoscape, for which functional enrichment analysis was applied with DAVID tools. A total of 293 and 133 DEGs were obtained for non-ischemic and ischemic heart failure, respectively. Two networks were established and then functional enrichment analysis revealed that "regulation of programmed cell death" was most significantly over-represented in common DEGs. Genes differentially expressed in non-ischemic and ischemic heart failure can be biomarkers to distinguish the two types of heart failure. Besides, these genes can be targets to develop treatments.


Capturing the holistic profile of high performance Olympic weightlifting development.
Recent expertise development studies have used retrospective recall methods to explore developmental biographies and/or practice histories of current or past athletes. This methodological approach limits the generalizability and trustworthiness of findings. As such, a gap exists for research exploring key multidisciplinary features in athlete development using prospective longitudinal research designs. The present research aimed to holistically model the development of talent in Olympic Weightlifting using such a design. We observed the holistic profiles of 29 junior weightlifting athletes longitudinally over a 10-month period, and subsequently classified six of the 23 athletes as high performing based on their performances in competitions up to 12 months following the study. This holistic profile was based on a framework of expertise development themes: (1) demographics and family sport participation, (2) anthropometrics and physiological factors, (3) psychosocial profiling, (4) sport participation history, and (5) weightlifting specific practice activities. A summary model was produced which selected a critical set of nine features that classified group membership with 91% average accuracy. Odds ratio calculations uncovered discriminating features in the holistic profiles of performance groups, from which empirically derived logical statements could inform the description of high-performance attainment.


Women's satisfaction with delivery care in Nairobi's informal settlements.
To quantify women's satisfaction with delivery care in informal settlements of Nairobi, Kenya, and to determine characteristics of women and delivery care associated with satisfaction. Household survey data analysis of 1266 women who delivered in health facilities in 2004 or 2005. Two densely populated informal settlements 7 and 12 km from Nairobi's center, where residents work primarily in the nearby industrial area or in the informal sector. Outcome Satisfaction was assessed by whether women would recommend the delivery care facility and deliver there again. Over half (56%) of women would both recommend and deliver again in the same facility. In multivariate analysis, women's satisfaction with delivery care was associated with greater provider empathy (OR = 3.68, 95% CI 2.27, 5.97). Women's satisfaction with delivery care was also associated with the pregnancy having been wanted (OR = 2.75, 95% CI 1.82, 4.14) or mistimed vs. unwanted. Women delivering at private facilities in the settlement near the industrial area were more satisfied than women delivering at private facilities in the more distant and marginalized settlement (OR = 2.12, 95% CI 1.45, 3.09). The association of women's satisfaction and provider empathy was stronger among women who experienced complications compared to those who did not. Health providers should be sensitized to the finding that unintended pregnancy is associated with lower satisfaction with delivery care. Maternal health programmes should focus on increasing provider empathy, especially for women who experience complications, in both private and government health facilities.


Plasma angiotensin-converting enzyme activity and left ventricular dilation after myocardial infarction.
Left ventricular dilation after acute myocardial infarction (MI) is mainly determined by infarct size. In addition, this detrimental structural adaptation seems to be augmented in patients with the ACE DD genotype. The ACE DD genotype is associated with increased ACE activity. The aim of the present study was to evaluate whether ACE activity per se may carry prognostic significance for subsequent left ventricular dilation as assessed by echocardiography during 1-year follow-up after acute MI. Left ventricular end-systolic and end-diastolic volume indexes were assessed by two-dimensional echocardiography. In 102 consecutive patients, plasma ACE activity was determined 3.7 +/- 0.1 hours after the onset of MI. In 64 of these patients, left ventricular volume indexes obtained at baseline and 1 year after MI were used for the present analysis. Patients were divided ino a group having low ACE activity (< or = IU/L, n = 15) and a group having high ACE activity (> 12 IU/L, n = 49). Infarct size was a significant predictor of the increase in left ventricular volume indexes (P = .0001) in these patients. Multivariate regression analysis, after correction for infarct size, demonstrated that elevated plasma ACE activity is a significant predictor of the increase in left ventricular end-diastolic and end-systolic volume indexes (P = .0006 and P = .02, respectively) 1 year after MI. Elevated plasma ACE activity determined soon after the onset of MI may be a significant predictor of the development of left ventricular dilation and may identify patients at risk.


Trends in alkali metal hydrosulfides: a combined Fourier transform microwave/millimeter-wave spectroscopic study of KSH (X1A').
The pure rotational spectrum of KSH (X(1)A') has been measured using millimeter-wave direct absorption and Fourier transform microwave (FTMW) techniques. This work is the first gas-phase experimental study of this molecule and includes spectroscopy of KSD as well. In the millimeter-wave system, KSH was synthesized in a DC discharge from a mixture of potassium vapor, H2S, and argon; a discharge-assisted laser ablation source, coupled with a supersonic jet expansion, was used to create the species in the FTMW instrument. Five and three rotational transitions in the range 3-57 GHz were recorded with the FTMW experiment for KSH and KSD, respectively, in the K(a) = 0 component; in these data, potassium quadrupole hyperfine structure was observed. Five to six transitions with K(a) = 0-5 were measured in the mm-wave region (260-300 GHz) for the two species. The presence of multiple asymmetry components in the mm-wave spectra indicates that KSH has a bent geometry, in analogy to other alkali hydrosulfides. The data were analyzed with an S-reduced asymmetric top Hamiltonian, and rotational, centrifugal distortion, and potassium electric quadrupole coupling constants were determined for both isotopolgues. The r0 geometry for KSH was calculated to be r(S-H) = 1.357(1) Å, r(K-S) = 2.806(1) Å, and θ(M-S-H) (°) = 95.0 (1). FTMW measurements were also carried out on LiSH and NaSH; metal electric quadrupole coupling constants were determined for comparison with KSH. In addition, ab initio computations of the structures and vibrational frequencies at the CCSD(T)/6-311++G(3df,2pd) and CCSD(T)/aug-cc-pVTZ levels of theory were performed for LiSH, NaSH, and KSH. Overall, experimental and computational data suggest that the metal-ligand bonding in KSH is a combination of electrostatic and covalent forces.


Willingness to Contribute to Bio-Larviciding in the Fight against Malaria: A Contingent Valuation Study among Rice Farmers in Rwanda.
There is broad consensus that successful and sustained larval source management (LSM) interventions, including bio-larviciding campaigns, require embeddedness in local community institutions. Ideally, these community structures should also be capable of mobilizing local resources to (co-)finance interventions. To date, farmer cooperatives, especially cooperatives of rice growers whose economic activity facilitates mosquito breeding, have remained under the radar in designing community-based bio-larviciding campaigns. This study explores the potential of rice farmer cooperatives in Bugesera district, Rwanda, to take up the aforementioned roles. To this purpose, we surveyed 320 randomly selected rice farmers who belonged to one of four rice cooperatives in the area and elicited their willingness-to-pay (WTP) for application of Bti, a popular bio-larvicide, in their rice paddies. Results from a (non-incentivized) bidding game procedure, which tested two alternative contribution schemes showed that financial contributions would be significantly different from zero and sufficient to carry a co-financing share of 15-25 per cent. A strong heterogeneity in mean WTP is revealed across cooperatives, in addition to variation among individual farmers, which needs to be anticipated when engaging farmer cooperatives in LSM.


From Chaos to Harmony: Responses and Signaling upon Microbial Pattern Recognition.
Pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs) are detected as nonself by host pattern recognition receptors (PRRs) and activate pattern-triggered immunity (PTI). Microbial invasions often trigger the production of host-derived endogenous signals referred to as danger- or damage-associated molecular patterns (DAMPs), which are also perceived by PRRs to modulate PTI responses. Collectively, PTI contributes to host defense against infections by a broad range of pathogens. Remarkable progress has been made toward demonstrating the cellular and physiological responses upon pattern recognition, elucidating the molecular, biochemical, and genetic mechanisms of PRR activation, and dissecting the complex signaling networks that orchestrate PTI responses. In this review, we present an update on the current understanding of how plants recognize and respond to nonself patterns, a process from which the seemingly chaotic responses form into a harmonic defense.


Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogenous disorder reported in Quebec caused by mutations in the SACS gene (chromosome 13q12). Recently, we identified a Tunisian kindred demonstrating linkage to the ARSACS locus. To report clinical, neurophysiological, and nerve biopsy findings in patients with autosomal recessive cerebellar ataxia related to the SACS gene in Tunisia. Genetic linkage analysis of patients with early-onset autosomal recessive cerebellar ataxia allowed the identification of 4 families from which 18 patients demonstrated linkage to the ARSACS locus. The patients were evaluated according to the International Cooperative Ataxia Rating Scale. Peripheral nerve conduction, sensory evoked potentials, and nerve biopsy were performed in most patients. The mean age at onset was 4.5 years. The clinical phenotype was stereotyped and associated with a progressive cerebellar syndrome, a pyramidal syndrome with brisk knee reflexes, and Babinski sign and absent ankle reflexes. The course of the disease varied among patients. Sensory evoked potentials showed severe posterior column involvement. Peripheral nerve investigations demonstrated axonal and demyelinating neuropathy. Four mutations, 2 missense and 2 nonsense, were found. In Tunisia, autosomal recessive cerebellar ataxia related to the SACS gene demonstrated a homogenous phenotype and heterogeneous allelic mutations.