Transcriptome response to glyphosate in sensitive and resistant soybean.
The majority of soybeans planted in the United States are resistant to glyphosate due to introduction of a gene encoding for a glyphosate-insensitive 5-enolypyruvylshikimate-3-phosphate synthase. Gene expression profiling was conducted using cDNA microarrays to address questions related to potential secondary effects of glyphosate. When glyphosate-sensitive plants were treated with glyphosate, 3, 170, and 311 genes were identified as having different transcript levels at 1, 4, and 24 h post-treatment (hpt), respectively. Differentially expressed genes were classified into functional categories, and their possible roles in response to glyphosate are briefly discussed. Gene expression profiling of glyphosate-resistant plants treated with glyphosate indicated that the plants were marginally affected at 1 hpt and then quickly adjusted to glyphosate treatment. Ten, four, and four genes were identified as differentially expressed at 1, 4, and 24 hpt. When gene expression profiles of cotyledons from developing seed were compared between the near-isogenic resistant and sensitive lines, two genes were identified as significantly differentially expressed out of 27000, which was less than the empirical false-discovery rate determined from a control experiment. Quantitative real-time reverse-transcribed Polymerase Chain Reaction was conducted on selected genes and yielded results consistent with those from the microarrays. Collectively, these data indicate that there are no major transcriptomic changes associated with currently used glyphosate-resistant soybean.


Microglia Exhibit Distinct Heterogeneity Rather than M1/M2 Polarization within the Early Stage of Acute Ischemic Stroke.
The classification of microglial M1/M2 polarization in the acute phase of ischemic stroke remains controversial, which has limited further advances in neuroprotective strategy. To thoroughly assess the microglial phenotypes, we made the middle cerebral artery occlusion model in mice to simulate the acute pathological processes of ischemic stroke from normal conditions to acute cerebral ischemia and then to the early reperfusion period. The temporal changes in gene profiles, cell subtypes, and microglial function were comprehensively analyzed using single-cell RNA sequencing. We identified 37,614 microglial cells and divided them into eight distinct subpopulations. Mic_home, Mic_pre1, and Mic_pre2 subpopulations were three clusters mainly composed of cells from the control samples, in which Mic_home was a homeostatic subpopulation characterized by high expression of Hpgd and Tagap, and Mic_pre1 and Mic_pre2 were two clusters with preliminary inflammatory activation characteristics marked by P2ry13 and Wsb1 respectively. Mic_M1L1 and Mic_M1L2 subpopulations exhibited M1-like polarization manifested by the upregulation of inflammatory genes after ischemic stroke, while the intrinsic heterogeneity on the level of inflammatory responses and neurotrophic support properties was observed. Moreover, we identified three unique clusters of cells with low inflammation levels. Mic_np1, Mic_np2, and Mic_np3 were characterized by high expression of Arhgap45, Rgs10, and Pkm respectively. However, these cells did not show significant M2-like characteristics and their classic microglia function was also attenuated. These subpopulations exhibited higher activation of neuropeptide functional pathways. At last, we performed cell-cell communication analysis and identified major couplings contributing to the interaction between microglia and other cell populations. In summary, our study elucidated the temporal heterogeneity of microglia in the acute phase of ischemic stroke, which may facilitate the identification of effective neuroprotective targets to curb ischemic damage at an early stage.


Design and synthesis of α-carboxy nucleoside phosphonate analogues and evaluation as HIV-1 reverse transcriptase-targeting agents.
The synthesis of the first series of a new class of nucleoside phosphonate analogues is described. Addition of a carboxyl group at the α position of carbocyclic nucleoside phosphonate analogues leads to a novel class of potent HIV reverse transcriptase (RT) inhibitors, α-carboxy nucleoside phosphonates (α-CNPs). Key steps in the synthesis of the compounds are Rh-catalyzed O-H insertion and Pd-catalyzed allylation reactions. In cell-free assays, the final products are markedly inhibitory against HIV RT and do not require phosphorylation to exhibit anti-RT activity, which indicates that the α-carboxyphosphonate function is efficiently recognized by HIV RT as a triphosphate entity, an unprecedented property of nucleoside monophosph(on)ates.


Sequencing and Characterisation of Complete Mitochondrial DNA Genome for Trigonopoma pauciperforatum (Cypriniformes: Cyprinidae: Danioninae) with Phylogenetic Consideration.
The Trigonopoma pauciperforatum or the redstripe rasbora is a cyprinid commonly found in marshes and swampy areas with slight acidic tannin-stained water in the tropics. In this study, the complete mitogenome sequence of T. pauciperforatum was first amplified in two parts using two pairs of overlapping primers and then sequenced. The size of the mitogenome is 16,707 bp, encompassing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organisation was detected between this species and other family members. The heavy strand accommodates 28 genes while the light strand houses the remaining nine genes. Most protein-coding genes utilise ATG as start codon except for COI gene which uses GTG instead. The terminal associated sequence (TAS), central conserved sequence block (CSB-F, CSB-D and CSB-E) as well as variable sequence block (CSB-1, CSB-2 and CSB-3) are conserved in the control region. The maximum likelihood phylogenetic tree revealed the divergence of T. pauciperforatum from the basal region of the major clade, where its evolutionary relationships with Boraras maculatus, Rasbora cephalotaenia and R. daniconius are poorly resolved as suggested by the low bootstrap values. This work contributes towards the genetic resource enrichment for peat swamp conservation and comprehensive in-depth comparisons across other phylogenetic researches done on the Rasbora-related genus.


Evolution of the enzymatic characteristics of C4 phosphoenolpyruvate carboxylase--a comparison of the orthologous PPCA phosphoenolpyruvate carboxylases of Flaveria trinervia (C4) and Flaveria pringlei (C3).
C4 phosphoenolpyruvate (P-pyruvate) carboxylases have evolved from ancestral C3 P-pyruvate carboxylases during the evolution of C4 photosynthesis (Lepiniec et al., 1994). To meet the requirements of a new metabolic pathway, the C4 enzymes have gained distinct kinetic and regulatory properties compared to C3 enzymes. Our interest is to deduce the structure responsible for these C4-specific properties. As a model system, the orthologous ppcA P-pyruvate carboxylases of Flaveria trinervia (C4) and Flaveria pringlei (C3) were investigated by expressing them in Escherichia coli using their cDNAs. The K(m) (P-pyruvate) was about ten times higher for the C4 enzyme (650 microM) than for the C3 enzyme (60 microM). The activation by glucose 6-phosphate, which was shown by a decrease in the K(m) (P-pyruvate), was about twice for the C4 enzyme and three times for the C3 enzyme. The C3 enzyme showed a very high sensitivity to L-malate with an I(0.5) (50% inhibition) value of 80 microM malate, whereas the C4 enzyme was much less sensitive with a I(0.5) value of 1.2 mM malate. To locate the structural positions responsible for these differences in kinetic and regulatory properties, chimeras of these 95% identical enzymes were made. In this study, the first 437 residues of the 966-amino-acid protein were interchanged. The results showed that the N-terminal part of the enzyme was responsible for a small but significant part of the kinetic difference observed between these two isoenzymes. Additionally, the results suggest that the N-terminus was the site for glucose 6-phosphate activation and was also responsible for the observed difference in activation by this sugar phosphate. The difference in inhibition by L-malate, however, is suggested to originate mainly from the C-terminal part of the enzyme.


A new weakly coordinating aluminate anion incorporating a chelating perfluoro-bis-anilido ligand.
The synthesis of the fully fluorinated bis-anilido ligand N,N'-bis-pentafluorophenyl-3,4,5,6-tetrafluorophenylene-1,2-diamine, 1 is described. Reaction of one or two equivalents of 1 with AlMe(3) gives aluminium compounds incorporating one or two ligands, the latter being the protonated form of a new weakly coordinating anion (WCA), 3-H. Alternatively, reaction of 1 with LiAlH(4) yields the lithium salt of this anion, 3-Li, which may be employed as a reagent for preparing the trityl and N,N-dimethylanilinium salts of the aluminate anion. All ion pairs are fully characterized and the use of 3-Ph(3)C to generate titanium-based alkyl cations is also described.


Mortality of filling station attendants.
Gasoline contains established human carcinogens, such as benzene. The health impact of exposure to this fuel, however, has not been fully elucidated. We report on the mortality of a cohort of 2665 filling station managers from the Latium region (Italy). This is the first workplace-based cohort of gas station attendants. However, only self-employed individuals were available for study (about 50% of the whole work force). The follow-up period extended from 1981 through 1992. The mortality experience of the cohort was compared with that of the regional population. The overall analysis for standardized mortality ratios (SMR) showed a significantly decreased mortality from all causes, mainly due to a deficit of cardiovascular diseases and malignant neoplasms. Nonsignificantly increased risks for esophageal cancer [SMR 241, 90% confidence interval (90% CI) 82-551], brain cancer (SMR 195, 90% CI 77-401) and non-Hodgkin's lymphoma (SMR 173, 90% CI 47-448) were found for the men; mortality due to lung cancer and leukemia was lower than expected, and no kidney cancer death was recorded. Among the attendants of small stations (characterized by a small number of employees and high sales of gasoline per full-time employee), the SMR values for esophageal cancer (for men SMR 351, 90% CI 120-803) and brain cancer (for men and women SMR 266, 90% CI 105-559) showed increased values. Filling station attendants are exposed to gasoline vapors and seem at risk of cancer of various sites. Due to the power limitations of this study, however, a precise estimate of the risk for many causes of death was not achievable. Further cohort studies of greater size are warranted.


[Not Available].
Introduction: Studies on infant dietary intake do not generally focus on the types of liquids consumed. Objective: To document by age and breastfeeding status, the types of liquids present in the diet of Mexican children under 1 year of age (< 1 y) who participated in the National Health and Nutrition Survey 2012 (ENSANUT-2012). Methods: Analysis of the infant < 1 y feeding practices from the ENSANUT-2012 survey in non-breastfed (non-BF) and breastfed (BF) infants by status quo for the consumption of liquids grouped in: water, formula, fortified LICONSA milk, nutritive liquids (NL; thin cereal-based gruel with water or milk and coffee with milk) and non-nutritive liquids (non-NL) as sugared water, water-based drinks, tea, beans or chicken broth, aguamieland coffee. In this infants < 1 y we analyzed the not grouped consumption of liquids in the first three days of life (newborns) from the mother's recall. Percentage and confidence intervals (95% CI) were calculated adjusting for survey design. Statistical differences were analyzed by Z test. Results: We observed a high consumption of human milk followed by formula (56.7%) and water (51.1%) in infants under 6 months of age (< 6 mo). The proportion of non-BF infants consuming non-NL was higher than for BF infants (p < 0.05). More than 60% of older infants (6 mo and < 1 y) consumed formula and were non-BF. In newborns formula consumption was predominant, followed by tea or infusion and water. Conclusions: Non-breast milk liquids are present undesirably in Mexican infants' diet and non-NL are consumed earlier than NL, revealing inadequate early dietary practices.


Results of primary repair of ulnar and median nerve injuries at the wrist: an evaluation of sensibility and motor recovery.
Sensibility and motor recovery after primary repair of ulnar and median nerve injuries at the wrist were evaluated in 21 patients (22 injuries). The outcome was graded according to the MRC system and correlated with the clinical results. Follow-up after an average of two years showed good clinical results in 10 cases, fair results in 9 and bad results in 3 cases. Primary neurorrhaphy can be considered as the treatment of choice for serious ulnar and median nerve injuries of the wrist in accordance with previous studies.


Rapid DNA mapping by fluorescent single molecule detection.
DNA mapping is an important analytical tool in genomic sequencing, medical diagnostics and pathogen identification. Here we report an optical DNA mapping strategy based on direct imaging of individual DNA molecules and localization of multiple sequence motifs on the molecules. Individual genomic DNA molecules were labeled with fluorescent dyes at specific sequence motifs by the action of nicking endonuclease followed by the incorporation of dye terminators with DNA polymerase. The labeled DNA molecules were then stretched into linear form on a modified glass surface and imaged using total internal reflection fluorescence (TIRF) microscopy. By determining the positions of the fluorescent labels with respect to the DNA backbone, the distribution of the sequence motif recognized by the nicking endonuclease can be established with good accuracy, in a manner similar to reading a barcode. With this approach, we constructed a specific sequence motif map of lambda-DNA. We further demonstrated the capability of this approach to rapidly type a human adenovirus and several strains of human rhinovirus.


Quality of Life as reported by school children and their parents: a cross-sectional survey.
Comprehensive evidence exists regarding the discrepancy between children's reports and parents' by proxy reports on emotional and behavioural problems. However, little is yet known about factors influencing the extent to which child self- and parent by proxy reports differ in respect of child Quality of Life (QoL). The aim of the study was to investigate the degree of discrepancy between child and parent by proxy reports as measured by two different QoL instruments. A representative Norwegian sample of 1997 school children aged 8-16 years, and their parents were studied using the Inventory of Life Quality (ILC) and the 'Kinder Lebensqualität Fragebogen' (KINDL). Child and parent reports were compared by t-test, and correlations were calculated by Pearson product moment coefficient. Psychometric aspects were examined in regard to both translated QoL instruments (internal consistency by Cronbach's alpha and test-retest reliability by intraclass correlation coefficients). Parents evaluated the QoL of their children significantly more positively than did the children. Correlations between mother-child and father-child reports were significant (p < 0.01) and similar but low to moderate (r = 0.32; and r = 0.30, respectively, for the KINDL, and r = 0.30 and r = 0.26, respectively, for the ILC). Mother and father reports correlated moderately highly (r = 0.54 and r = 0.61 for the KINDL and ILC, respectively). No significant differences between correlations of mother-daughter/son and father-daughter/son pairs in regard to reported child QoL were observed on either of the two instruments. In the present general population sample, parents reported higher child QoL than did their children. Concordance between child and parent by proxy report was low to moderate. The level of agreement between mothers and fathers in regard to their child's QoL was moderate. No significant impact of parent and child gender in regard to agreement in ratings of child QoL was found. Both the child and parent versions of the Norwegian translations of the KINDL and ILC can be used in surveys of community populations, but in regard to the self-report of 9-10 years old children, only the KINDL total QoL scale or the ILC are recommended.


[Cortisol metabolism in hypertensive patients during the crisis period].
The examination was conducted in 67 patients with Stage II essential hypertension, aged 29 to 60 years (13 males and 54 females). Cortisol metabolism was assessed on the basis of a study of daily urine excretions of tetrahydrocortisol, tetrahydrocortisone, cortisol, cortisone, 17-oxy-11-desoxycortisol and of their ratio. It is found that in patients with Stage II essential hypertension, beyond the period of exacerbation, cortisol metabolism and the glucocorticoid function of the adrenal cortex are unchanged. During crises the gluococorticoid function of the adrenal cortex is activated, and some changes develop in cortisol metabolism. The severity of the crisis does not affect cortisol metabolism, but results in a growing total secretory activity of the adrenal cortex.


A DFT study of IRMOF-3 catalysed Knoevenagel condensation.
It has been recently reported that IRMOF-3 [Gascon et al., J. Catal, 2009, 261, 75] may behave as a basic catalyst, active in the Knoevenagel condensation. In particular, it has been shown that the basicity of aniline-like amino moieties is enhanced, along with the catalytic activity, when incorporated into MOF structures. The computational study here was aimed at finding possible atomistic explanations of the increased basicity and catalytic activity of the IRMOF-3 embedded aniline groups, experimentally claimed. It was, moreover, aimed at guessing a reaction mechanism for the IRMOF-3 catalysed Knoevenagel condensation of benzaldehyde and ethyl-cyanoacetate. Within the DFT framework we have studied structure and basicity properties of IRMOF-3 and we have analysed the energetics of the catalytic cycle as well as of possible deactivation paths, including it. The increased basicity of IRMOF-3 over other amminic catalysts has been explained via the formation of protonated conjugate derivatives, involving hydrogen-bonds and originating quasi-planar 6-term rings. Several plausible reaction steps have been moreover taken into account and a mechanism for the Knoevenagel condensation, including catalyst deactivation, has been proposed for aniline molecules and embedded aniline moieties. This allowed us to suggest that the increased IRMOF-3 activity, as a basic catalyst, should be mostly related to its water adsorption ability, preserving the properties of the catalytically active amino moieties.


[Role of the hypothalamus in the reflex regulation of cardiac activity].
A review of literary and own experimental data is given. More adequate method in the study of the hypothalamic heart regulation is the investigation of the hypothalamic influences on the cardiac reflexes. The necessity of the experiments on the unanesthetized unrestrained animals is underlined. The dual modulating hypothalamic influences existing already in fishes having been revealed on the unanesthetized animals. The character of the modulating influence is determinated to a certain extent by the cardiac reflex intensity: small responses are increased, larger ones are reduced. The extension of system regions involved into the reflex response pattern at the increase of the degree of temperature effect of venous blood on heart has been discovered in unanesthetized unrestrained cats.


Does Race Affect Outcomes in Total Joint Arthroplasty?
Several studies suggest worse surgical outcomes among racial/ethnic minorities. There is a paucity of research on preoperative and postoperative pain, general health, and disease-specific measures in which race is the main subject of investigation; furthermore, the results are not conclusive. (1) Do black patients have more severe or more frequent preoperative pain, well-being, general health, and disease-specific scores when compared with white patients? (2) Are there differences between black patients and white patients after hip or knee arthroplasty on those same measures? In this retrospective study, we used an institutional arthroplasty registry to analyze data on 2010 primary arthroplasties (1446 knees and 564 hips) performed by one surgeon at a single institution. Cases from patients self-identifying as black (n = 105) and white (n = 1905) were compared (controlling for confounders, including age and ethnicity) on the following preoperative and postoperative patient-oriented outcomes: pain intensity/frequency as measured by a visual analog scale (VAS), Quality of Well-Being (QWB-7), SF-36, and WOMAC scores. T-tests, chi square, and multivariate analysis of covariance were used. Alpha was set at 0.05. Postoperative analysis was performed only on those cases that had a minimum followup of 1 year (mean, 3.5 years; range, 1-9 years). Of the 2010 arthroplasties, 37% (39 of 105) of those cases performed in black patients and 64% (1219 of 1905) of those performed in white patients were included in the final postoperative model (multivariate analysis of covariance). Black patients had more severe preoperative pain intensity (VAS: 8 ± 1.8 versus 8 ± 2.0, mean difference = 0.76 [95% confidence interval {CI}, 0.34-1.1], p < 0.001). Black patients also had worse well-being scores (QWB-7: 0.527 ± 0.04 versus 0.532 ± 0.05, mean difference = -0.01 [CI, -0.02 to 0.00], p = 0.037). Postoperatively, pain intensity (VAS: 1 ± 3.1 versus 1 ± 1.8, mean difference= 0.8 [CI, 0.19-1.4], p= 0.010) and (QWB-7: 0.579 ± 0.09 versus 0.607 ± 0.11, mean difference= -0.049 [CI, -0.08 to -0.01], p = 0.008) were different but without clinical significance. Black patients underwent surgery earlier in life and with different preoperative diagnoses when compared with white patients. Black patients had worse preoperative baseline pain, well-being, general health, and disease-specific scores as well as worse postoperative scores. However, these differences were very narrow and without clinical significance. Notwithstanding, the relations of race with outcomes remain complex. Further investigations to recognize disparities and minimize or address them are warranted. Level III, prognostic study.


The ground-state potential energy curve of the radium dimer from relativistic coupled cluster calculations.
The potential energy curve for the ground-state of radium dimer (Ra2) is provided by means of atomic and molecular relativistic coupled cluster calculations. The short-range part of this curve is defined by an equilibrium bond length of 5.324 Å, a dissociation energy of 897 cm(-1), and a harmonic vibrational frequency of 20.5 cm(-1). The asymptotic behavior at large interatomic distances is characterized by the van der Waals coefficients C6 = 5.090 × 10(3), C8 = 6.978 × 10(5), and C10 = 8.786 × 10(7) atomic units. The two regions are matched in an analytical potential to provide a convenient representation for use in further calculations, for instance, to model cold collisions between radium atoms. This might become relevant in future experiments on ultracold, optically trapped, radioactive radium atoms that are used to search for a permanent electric dipole moment.


Evaluation of molecular breast imaging in women undergoing myocardial perfusion imaging with Tc-99m sestamibi.
Our objective was to explore the potential benefits of molecular breast imaging (MBI) as a screening technique in women undergoing stress myocardial perfusion studies. MBI was offered to women receiving Tc-99m sestamibi injection for myocardial perfusion stress testing. During the required waiting period after stress isotope injection, MBI was performed using a dedicated breast imaging gamma camera system. MBI examinations were interpreted by breast radiologists, with review of a recent mammogram in cases with positive MBI. Of 322 women enrolled, 313 completed MBI, comprising 5 with known breast cancer, 2 with known high-risk benign breast lesions, and 306 who were asymptomatic for breast disease with a recent negative mammogram. Analysis was limited to the 306 patients with no known breast disease. MBI was positive in 22 of 306, giving a recall rate of 7.2% (95% confidence interval [CI] 4.8-10.6]. MBI detected 4 new cancers, resulting in a supplemental diagnostic yield of 13.1/1000 women screened (95% CI 5.1-33.2). The number of cancers diagnosed per abnormal MBI examinations (PPV(1)) was 18% (4 of 22) (95% CI 7.3-38.5), and the number diagnosed per MBI-prompted biopsies (PPV(3)) was 44% (4 of 9) (95% CI 18.9-73.3). The addition of MBI to clinically indicated stress myocardial perfusion imaging studies in women results in a high diagnostic yield of newly detected breast cancers while generating a low rate of additional unnecessary workup.


Are Rib Versus Spine Anchors Protective Against Breakage of Growing Rods?
Retrospective multicenter, case-control study. To compare the risks of rod breakage and anchor complications between distraction-based growing rods with proximal spine versus rib anchors. Rod breakage is a known complication of distraction-based growing rod instrumentation. A total of 176 patients met inclusion criteria: minimum 2-year follow-up, younger than age 9 years at index surgery, non-Vertical Expandable Prosthetic Titanium Rib distraction-based growing rods, and known anchor locations. Mean follow-up was 56 months (range, 24-152 months). Survival analyses using Cox proportional hazards model (accounting for varying lengths of follow-up) of rod breakage, anchor complications, preoperative Cobb angle, number of growing rods, age, and number of levels instrumented were performed using a significance level of p < .05. Thirty-four patients had rib-anchored growing rods and 142 had spine-anchored growing rods. This analysis found that proximal rib-anchored growing rods have a 23% risk of lifetime rod breakage compared with spine-anchored growing rods (6% vs. 29%) (p = .041) without a significant increase in risk of anchor complications (38% vs. 33%) (p = .117). The number of implanted rods (p = .839), age (p = .649), and number of instrumented levels (p = .447) were not statistically significant regarding rod breakage risk, although higher preoperative Cobb angles were significant (p = .014). Preoperative Cobb angle appears to be the most influential factor in determining whether growing rods break (p = .014). Univariate analysis found that rib anchors were associated with less than one-fourth the risk of rod breakage than spine anchors (p = .04) but multivariate analysis found no significant association between anchors and rod breakage (p = .07). This trend suggests that rib-anchored growing rod systems may be associated with less rod breakage because the system is less rigid as a result of some "slop" at the hook-rib interface, as well as the normal motion of the costovertebral joint.


Outcomes of appendectomy in elderly veteran patients.
Some studies indicate that noncomplicated acute appendicitis might be treated exclusively with antibiotics instead of an appendectomy. This study was undertaken to assess outcomes in elderly veterans and to determine if operative intervention would lead to substantial complications such that a nonoperative strategy should be investigated. A retrospective, single-institution analysis was conducted of patients who underwent an appendectomy at the VA North Texas Health Care System over a period of 12 years (from July 2005 to June 2017). Patients who underwent an appendectomy for cancer, interval appendectomy, exploratory laparotomy for perforated appendicitis, or appendectomy as part of another major operation were excluded from the study. Patients were then grouped as elderly (≥60 years old) and young (<60 years old), and differences in outcome were assessed. Univariate and multivariate analyses were also performed to determine if age and comorbid conditions were independent predictors of complications in both cohorts. Of patients who underwent an appendectomy for acute appendicitis (n = 257, male = 90.7%, age = 45.4 ± standard deviation 15.6 years, body mass index = 30.3 ± 6.3 kg/m2), 195 were young (38.7 ± 11.2 years old) and 62 elderly (66 ± 5 years old). More patients were male in the elderly cohort (98.4% vs 88%; P = .01). The incidence of gangrenous and perforated appendicitis was greater in elderly patients (11.3% and 14.4% vs 24 % and 40%, P < .01 each). Diabetes and hypertension, as well as a history of cardiac, pulmonary, and renal diseases, were more than 2-fold greater in older patients. Complications and 30-day readmission rates were similar in both groups (young vs elderly: 7.2% and 9% vs 9.7% and 11%, P > .5 each). Logistic regression analysis showed that age and American Society of Anesthesia level were not independent predictors of complications. A history of cardiac disease and open operation independently predicted complications regardless of age. Unexpected malignancy was 3% in the elderly and 1.5% in the young cohort (P = .6) CONCLUSION: Complicated appendicitis is more common in elderly patients. Appendectomy in elderly veteran patients has a low rate of complications similar to younger patients and the private sector. Operative intervention in this group of patients is not prohibitive. Further studies are needed to determine if nonoperative intervention is noninferior to an appendectomy in this high-risk patient population.


Recognition specificity of the duplicated segments present in Clostridium thermocellum endoglucanase CelD and in the cellulosome-integrating protein CipA.
The binding specificity of the duplicated segments borne by Clostridium thermocellum endoglucanase CelD and by the cellulosome-integrating protein CipA was investigated. The fusion protein CelC-DSCelD, in which the duplicated segment of CelD was fused to the COOH terminus of endoglucanase CelC, bound with an affinity of 4.7 x 10(7) M-1 to the fusion protein MalE-RDCipA, in which the seventh receptor domain of CipA was grafted onto the COOH terminus of the Escherichia coli maltose-binding protein MalE. The affinity of CelC-DSCelD for the homologous chimeric protein MalE-RDORF3p, carrying the receptor of the surface protein ORF3p, was 6.9 x 10(6) M-1. The fusion protein CelC-DSCipA, in which the duplicated segment of CipA was grafted onto the COOH terminus of CelC, did not bind detectably to MalE-RDCipA or MalE-RDORF3p. However, Western blotting (immunoblotting) experiments indicated that the duplicated segment of CipA was able to bind to a set of C. thermocellum proteins which are different from those recognized by the duplicated segment of CelD. These results argue against the hypothesis that ORF3p interacts with the duplicated segment of CipA. More probably, ORF3p binds to individual cellulases and hemicellulases harboring duplicated segments.


The switch complex ArlCDE connects the chemotaxis system and the archaellum.
Cells require a sensory system and a motility structure to achieve directed movement. Bacteria and archaea possess rotating filamentous motility structures that work in concert with the sensory chemotaxis system. This allows microorganisms to move along chemical gradients. The central response regulator protein CheY can bind to the motor of the motility structure, the flagellum in bacteria, and the archaellum in archaea. Both motility structures have a fundamentally different protein composition and structural organization. Yet, both systems receive input from the chemotaxis system. So far, it was unknown how the signal is transferred from the archaeal CheY to the archaellum motor to initiate motor switching. We applied a fluorescent microscopy approach in the model euryarchaeon Haloferax volcanii and shed light on the sequence order in which signals are transferred from the chemotaxis system to the archaellum. Our findings indicate that the euryarchaeal-specific ArlCDE are part of the archaellum motor and that they directly receive input from the chemotaxis system via the adaptor protein CheF. Hence, ArlCDE are an important feature of the archaellum of euryarchaea, are essential for signal transduction during chemotaxis and represent the archaeal switch complex.


Comparative genomic analysis of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis.
The Leishmania (Viannia) braziliensis complex is responsible for most cases of New World tegumentary leishmaniasis. This complex includes two closely related species but with different geographic distribution and disease phenotypes, L. (V.) peruviana and L. (V.) braziliensis. However, the genetic basis of these differences is not well understood and the status of L. (V.) peruviana as distinct species has been questioned by some. Here we sequenced the genomes of two L. (V.) peruviana isolates (LEM1537 and PAB-4377) using Illumina high throughput sequencing and performed comparative analyses against the L. (V.) braziliensis M2904 reference genome. Comparisons were focused on the detection of Single Nucleotide Polymorphisms (SNPs), insertions and deletions (INDELs), aneuploidy and gene copy number variations. We found 94,070 variants shared by both L. (V.) peruviana isolates (144,079 in PAB-4377 and 136,946 in LEM1537) against the L. (V.) braziliensis M2904 reference genome while only 26,853 variants separated both L. (V.) peruviana genomes. Analysis in coding sequences detected 26,750 SNPs and 1,513 indels shared by both L. (V.) peruviana isolates against L. (V.) braziliensis M2904 and revealed two L. (V.) braziliensis pseudogenes that are likely to have coding potential in L. (V.) peruviana. Chromosomal read density and allele frequency profiling showed a heterogeneous pattern of aneuploidy with an overall disomic tendency in both L. (V.) peruviana isolates, in contrast with a trisomic pattern in the L. (V.) braziliensis M2904 reference. Read depth analysis allowed us to detect more than 368 gene expansions and 14 expanded gene arrays in L. (V.) peruviana, and the likely absence of expanded amastin gene arrays. The greater numbers of interspecific SNP/indel differences between L. (V.) peruviana and L. (V.) braziliensis and the presence of different gene and chromosome copy number variations support the classification of both organisms as closely related but distinct species. The extensive nucleotide polymorphisms and differences in gene and chromosome copy numbers in L. (V.) peruviana suggests the possibility that these may contribute to some of the unique features of its biology, including a lower pathology and lack of mucosal development.


Microarray assessment of virulence, antibiotic, and heavy metal resistance in an agricultural watershed creek.
Potential risks associated with impaired surface water quality have commonly been evaluated by indirect description of potential sources using various fecal microbial indicators and derived source-tracking methods. These approaches are valuable for assessing and monitoring the impacts of land-use changes and changes in management practices at the source of contamination. A more detailed evaluation of putative etiologically significant genetic determinants can add value to these assessments. We evaluated the utility of using a microarray that integrates virulence genes with antibiotic and heavy metal resistance genes to describe and discriminate among spatially and seasonally distinct water samples from an agricultural watershed creek in Eastern Ontario. Because microarray signals may be analyzed as binomial distributions, the significance of ambiguous signals can be easily evaluated by using available off-the-shelf software. The FAMD software was used to evaluate uncertainties in the signal data. Analysis of multilocus fingerprinting data sets containing missing data has shown that, for the tested system, any variability in microarray signals had a marginal effect on data interpretation. For the tested watershed, results suggest that in general the wet fall season increased the downstream detection of virulence and resistance genes. Thus, the tested microarray technique has the potential to rapidly describe the quality of surface waters and thus to provide a qualitative tool to augment quantitative microbial risk assessments.


Measuring Flourishing Among Internal Medicine and Psychiatry Residents.
Many residents experience burnout, prompting national attention to well-being; however, well-being is not merely the absence of burnout. A recently developed measure of flourishing may provide insight on this important topic. We investigated flourishing in a sample of medical residents. Internal medicine residents and psychiatry residents at 2 residency programs responded to a cross-sectional online survey (December 2017-February 2018), which focused on the Flourish Index (FI) and Secure Flourish Index (SFI). Both measures generate scores ranging from a low of 0 to a high of 10. Participants were queried about quality of life, burnout, work-life balance, empathic concern, and sociodemographic characteristics. Simple and multiple linear regressions were performed to examine the relationship between FI/SFI and other variables. The response rate was 92% (92 of 101). Participants were found to have a mean FI score of 6.8 (SD = 1.6) and mean SFI score of 6.9 (SD = 1.6). Low quality of life, low work-life balance satisfaction, high emotional exhaustion, lower empathic concern, and having a pet were all significantly associated with lower FI scores (R2 = 0.59; F[14, 69] = 7.10; P < .0001), indicating lesser flourishing, controlling for other variables. Similarly, low quality of life, high emotional exhaustion, lower empathic concern, and having a pet were all significantly associated with lower SFI scores (R2 = 0.55; F[14, 69] = 6.06; P < .0001), controlling for other variables. In this sample, the flourishing indices were associated with well-being and burnout metrics.


Electro-osmosis of nematic liquid crystals under weak anchoring and second-order surface effects.
Advent of nematic liquid crystal flows has attracted renewed attention in view of microfluidic transport phenomena. Among various transport processes, electro-osmosis stands as one of the efficient flow actuation mechanisms through narrow confinements. In the present study, we explore the electrically actuated flow of an ordered nematic fluid with ionic inclusions, taking into account the influences from surface-induced elasticity and electrical double layer (EDL) phenomena. Toward this, we devise the coupled flow governing equations from fundamental free-energy analysis, considering the contributions from first- and second-order elastic, dielectric, flexoelectric, charged surface polarization, ionic and entropic energies. The present study focuses on the influence of surface charge and elasticity effects in the resulting linear electro-osmosis through a slit-type microchannel whose surfaces are chemically treated to display a homeotropic-type weak anchoring state. An optical periodic stripe configuration of the nematic director has been observed, especially for higher electric fields, wherein the Ericksen number for the dynamic study is restricted to the order of unity. Contrary to the isotropic electrolytes, the EDL potential in this case was found to be dependent on the external field strength. Through a systematic investigation, we brought out the fact that the wavelength of the oscillating patterns is dictated mainly by the external field, while the amplitude depends on most of the physical variables ranging from the anchoring strength and the flexoelectric coefficients to the surface charge density and electrical double layer thickness.


Protocol for treatment of typical urinary tract infection: criteria for antimicrobial selection.
Criteria for selecting an appropriate drug for treatment of urinary tract infection are based on therapeutic goals. A major criterion is to choose an antimicrobial that will not affect the patient's fecal and vaginal flora. Low cost is another important criterion. It is unnecessary to select an expensive antimicrobial when highly effective agents are available at low cost. High urinary concentration is the third goal of therapy and a major criterion for selecting an appropriate drug. To apply these selection criteria in clinical practice, use a criteria-based classification. Choose the agent highest on the following lists for which the patient shows no sensitivity: Class I, nitrofurantoin macrocrystals and penicillin VK; Class II, carbenicillin; Class III, amoxicillin; Class IV, trimethoprim-sulfamethoxazole and cephalosporins; Class V, ampicillin, tetracycline, norfloxacin.


[Peripheral primitive neuroectodermal tumor -- PNET].
The authors describe three cases of peripheral primitive neuroectodermal tumor. The tumor was found in soft tissues of the crus, shoulder girdle and perineum, and was also located paravertebrally and epidurally at the level of L1-L2 vertebrae. Radiological findings were not specific for this disease. The results of imaging methods (sonography, CT, MRI, DSA) were important for the assessment of tumor size, its boundary and invasion of the surrounding tissues, and for the evaluation of tumor response to therapy and detection of recurrent disease. The PNET diagnosis was based on immunohistochemical, biochemical and cytogenetic examinations. One patient died 5 months after the first clinical signs were manifested; the two patients surviving for 2 and 1 3/4 years after first sign manifestation, respectively, remained in the care of cancer specialists. Key words: skeletal Ewing's sarcoma, extra-skeletal Ewing's sarcoma, Ewing's sarcoma family of tumors, peripheral primitive neuroectodermal tumor.


Subacromial Decompression Yields a Better Clinical Outcome Than Therapy Alone: A Prospective Randomized Study of Patients With a Minimum 10-Year Follow-up.
The long-term outcome after the treatment of subacromial impingement syndrome (SAIS) with either nonsurgical or surgical methods has not been thoroughly investigated. Hypothesis/Purpose: The purpose was to evaluate the long-term clinical outcome and the presence of rotator cuff injuries and osteoarthritis (OA) after the surgical and nonsurgical treatment of SAIS. The hypothesis was that, at a minimum 10 years after the initial treatment, patients who had undergone acromioplasty would have a better clinical outcome and run a lower risk of developing rotator cuff ruptures and OA as compared with those treated with physical therapy. Randomized controlled trial; Level of evidence, 2. Eighty-seven patients with SAIS were randomized to 3 groups: open acromioplasty (open surgery group [OSG]), arthroscopic acromioplasty (arthroscopic surgery group [ASG]), and nonsurgical treatment (physical therapy group [PTG]). The Constant score, the Watson and Sonnabend score, and the 36-Item Short Form Health Survey (SF-36) questionnaire were used as outcome measurements. Furthermore, bilateral ultrasound examinations were performed to detect rotator cuff ruptures and bilateral radiographs to detect OA. Sixty-six patients (76%) attended the clinical follow-up at least 10 years after the initial treatment. The groups were demographically comparable at baseline. The Constant score improved significantly at follow-up for the OSG ( P = .003) and ASG ( P = .011), while no significant improvement was detected for the PTG. The OSG revealed a significant improvement versus the PTG at follow-up ( P = .011); otherwise, no significant differences were found. For the Watson and Sonnabend score, the OSG revealed a significant improvement in 13 of 14 questions. The corresponding finding was made for the ASG and PTG in 9 of 14 questions ( P = .14). According to ultrasound, 1 of 20 patients in the OSG had a full-thickness rotator cuff rupture on the index side. The corresponding finding was made for 1 of 18 patients in the ASG and 4 of 28 in the PTG ( P = .29). Per the radiographs, 3 of 20 patients in the OSG had moderate or severe OA in the index shoulder. The corresponding finding was made for 1 of 18 patients in the ASG and 0 of 28 in the PTG ( P = .12). After a minimum 10 years of follow-up, the surgical treatment of SAIS appears to render better clinical results than physical therapy alone. No significant differences were found among the groups in terms of the presence of full-thickness rotator cuff ruptures and OA.


Haptic communication between humans is tuned by the hard or soft mechanics of interaction.
To move a hard table together, humans may coordinate by following the dominant partner's motion [1-4], but this strategy is unsuitable for a soft mattress where the perceived forces are small. How do partners readily coordinate in such differing interaction dynamics? To address this, we investigated how pairs tracked a target using flexion-extension of their wrists, which were coupled by a hard, medium or soft virtual elastic band. Tracking performance monotonically increased with a stiffer band for the worse partner, who had higher tracking error, at the cost of the skilled partner's muscular effort. This suggests that the worse partner followed the skilled one's lead, but simulations show that the results are better explained by a model where partners share movement goals through the forces, whilst the coupling dynamics determine the capacity of communicable information. This model elucidates the versatile mechanism by which humans can coordinate during both hard and soft physical interactions to ensure maximum performance with minimal effort.


Voiceless alveolar stop coarticulation in typically developing 5-year-olds and 13-year-olds.
In this study, vowel-on-consonant lingual coarticulation at [t] closure offset was compared in 5-year-old children and 13-year-old adolescents. The study aimed to establish whether, by the end of the closure, children from the younger age group adjust the tongue shape to the following vowels to the same extent as adolescents. Ten 5-year-olds and ten 13-year-olds, all speakers of Scottish Standard English, produced [t]-vowel syllables with the vowels [i] and [a], in a carrier phrase. Measures of tongue shape based on midsagittal ultrasound imaging data were used to compare anticipatory coarticulation and within-speaker variability across groups. Both age groups changed the extent of tongue dorsum bunching in order to coarticulate the consonant with the following vowels. The 5-year-old children, unlike the adolescents, did not consistently modify the bunching location within the tongue curve to accommodate the tongue shape to that of the upcoming vowel. Token-to-token variability was significantly greater in the younger age group. The results suggest that vowel-on-[t] coarticulatory patterns produced by typically developing children are affected by the development of motor control, with articulatory constraints on the tongue limiting the extent of lingual coarticulation in 5-year-old children. The findings on typical coarticulation development are relevant for clinical practice, and they highlight the need for more detailed descriptions of how phonetic characteristics of speech sounds affect coarticulation throughout childhood.


The management of melanoma and nonmelanoma skin cancer: a review for the primary care physician.
In the United States, the incidence of skin cancer is greater than that of all other cancers combined, and early diagnosis can be lifesaving. A substantial public health concern, skin cancer is increasingly being diagnosed and managed by primary care physicians. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) (known collectively as nonmelanoma skin cancer) and malignant melanoma are the most common cutaneous malignancies. Shave biopsy is usually performed if BCC is suspected; punch biopsy is preferred if SCC is thought to be present. The choice of biopsy techniques depends on the presumed depth of the lesion. Treatment has 3 goals: complete eradication of the cancer and preservation or restoration of normal function and cosmesis. Risk of recurrence or metastasis determines whether the tumor is high risk or low risk. Based on the level of risk, treatment options are considered, including whether the patient can be treated by a primary care physician or should be referred to a dermatologist. Choice of treatment approach depends on the tumor's location, size, borders, and growth rate. The standard treatment approaches are superficial ablative techniques (electro-desiccation and curettage and cryotherapy) used primarily for low-risk tumors and full-thickness techniques (Mohs micrographic surgery, excisional surgery, and radiotherapy) used to treat high-risk tumors. Removal of the entire tumor is essential to limit and prevent tumor recurrence.


C-terminal tail length guides insertion and assembly of membrane proteins.
A large number of newly synthesized membrane proteins in the endoplasmic reticulum (ER) are assembled into multiprotein complexes, but little is known about the mechanisms required for assembly membrane proteins. It has been suggested that membrane chaperones might exist, akin to the molecular chaperones that stabilize and direct the assembly of soluble protein complexes, but the mechanisms by which these proteins would bring together membrane protein components is unclear. Here, we have identified that the tail length of the C-terminal transmembrane domains (C-TMDs) determines efficient insertion and assembly of membrane proteins in the ER. We found that membrane proteins with C-TMD tails shorter than ∼60 amino acids are poorly inserted into the ER membrane, which suggests that translation is terminated before they are recognized by the Sec61 translocon for insertion. These C-TMDs with insufficient hydrophobicity are post-translationally recognized and retained by the Sec61 translocon complex, providing a time window for efficient assembly with TMDs from partner proteins. Retained TMDs that fail to assemble with their cognate TMDs are slowly translocated into the ER lumen and are recognized by the ER-associated degradation (ERAD) pathway for removal. In contrast, C-TMDs with sufficient hydrophobicity or tails longer than ∼80 residues are quickly released from the Sec61 translocon into the membrane or the ER lumen, resulting in inefficient assembly with partner TMDs. Thus, our data suggest that C-terminal tails harbor crucial signals for both the insertion and assembly of membrane proteins.


Distribution of Lettuce Big-Vein Incidence Under Three Irrigation Systems.
Spatial patterns of lettuce big-vein (LBV) incidence under furrow, sprinkler, and subsurface drip irrigation systems were determined. Because LBV pathogen is a virus and is vectored by the soilborne chytrid Olpidium brassicae, different irrigation systems likely affect the movement of the vector and were hypothesized to result in different distribution patterns and levels of the disease. Lettuce plants were mapped by recording the location of each LBV-infected or healthy plant in arbitrarily selected plots of sizes 16 by 30, 20 by 30, and 18 by 50 m in Salinas, Gonzales, and Santa Maria in California. Data were arrayed into different quadrat sizes by rearrangement, and disease incidence was calculated for each quadrat. Frequency distribution analysis and spatial autocorrelation analyses were performed on this data. LBV incidence was aggregated in all furrow-irrigated fields, four of five subsurface drip-irrigated fields, and two of three sprinkler-irrigated fields. The remaining fields had a random distribution. As the quadrat size increased, index of aggregation decreased, and vice versa. In fields under sprinkler irrigation, regardless of whether the spatial pattern of LBV was random or aggregated, no directional orientation occurred. However, under furrow or subsurface drip irrigation, the aggregation mostly occurred across the rows. Although irrigation type influenced LBV distribution pattern and incidence in lettuce fields, the differential effects of irrigation type on vector O. brassicae could not be discerned in this study. The sprinkler irrigation practiced in lettuce production until thinning may influence the vector distribution and the subsequent irrigation methods adapted for the remainder of the season in individual fields may play a significant role in disease incidence.


Codeine, alone and with paracetamol (acetaminophen), for cancer pain.
Pain is very common in patients with cancer. Opioid analgesics, including codeine, play a significant role in major guidelines on the management of cancer pain, particularly for mild to moderate pain. Codeine is widely available and inexpensive, which may make it a good choice, especially in low-resource settings. Its use is controversial, in part because codeine is not effective in a minority of patients who cannot convert it to its active metabolite (morphine), and also because of concerns about potential abuse, and safety in children. To determine the efficacy and safety of codeine used alone or in combination with paracetamol for relieving cancer pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2014, Issue 2), MEDLINE and EMBASE from inception to 5 March 2014, supplemented by searches of clinical trial registries and screening of the reference lists of the identified studies and reviews in the field. We sought randomised, double-blind, controlled trials using single or multiple doses of codeine, with or without paracetamol, for the treatment of cancer pain. Trials could have either parallel or cross-over design, with at least 10 participants per treatment group. Studies in children or adults reporting on any type, grade, and stage of cancer were eligible. We accepted any formulation, dosage regimen, and route of administration of codeine, and both placebo and active controls. Two review authors independently read the titles and abstracts of all studies identified by the searches and excluded those that clearly did not meet the inclusion criteria. For the remaining studies, two authors read the full manuscripts and assessed them for inclusion. We resolved discrepancies between review authors by discussion. Included studies were described qualitatively, since no meta-analysis was possible because of the small amount of data identified, and clinical and methodological between-study heterogeneity. We included 15 studies including 721 participants with cancer pain due to diverse types of malignancy. All studies were performed on adults; there were no studies on children. The included studies were of adequate methodological quality, but all except for one were judged to be at a high risk of bias because of small study size, and six because of methods used to deal with missing data or high withdrawal rates. Three studies used a parallel group design; the remainder were cross-over trials in which there was an adequate washout period, but only one reported results for treatment periods separately.Twelve studies used codeine as a single agent and three combined it with paracetamol. Ten studies included a placebo arm, and 14 included one or more of 16 different active drug comparators or compared different routes of administration. Most studies investigated the effect of a single dose of medication, while five used treatment periods of one, seven or 21 days. Most studies used codeine at doses of 30 mg to 120 mg.There were insufficient data for any pooled analysis. Only two studies reported our preferred responder outcome of 'participants with at least 50% reduction in pain' and two reported 'participants with no worse than mild pain'. Eleven studies reported treatment group mean measures of pain intensity or pain relief; overall for these outcome measures, codeine or codeine plus paracetamol was numerically superior to placebo and equivalent to the active comparators.Adverse event reporting was poor: only two studies reported the number of participants with any adverse event specified by treatment group and only one reported the number of participants with any serious adverse event. In multiple-dose studies nausea, vomiting and constipation were common, with somnolence and dizziness frequent in the 21-day study. Withdrawal from the studies, where reported, was less than 10% except in two studies. There were three deaths, in all cases due to the underlying cancer. We identified only a small amount of data in studies that were both randomised and double-blind. Studies were small, of short duration, and most had significant shortcomings in reporting. The available evidence indicates that codeine is more effective against cancer pain than placebo, but with increased risk of nausea, vomiting, and constipation. Uncertainty remains as to the magnitude and time-course of the analgesic effect and the safety and tolerability in longer-term use. There were no data for children.


O2 Activation by Non-Heme Thiolate-Based Dinuclear Fe Complexes.
Iron centers featuring thiolates in their metal coordination sphere (as ligands or substrates) are well-known to activate dioxygen. Both heme and non-heme centers that contain iron-thiolate bonds are found in nature. Investigating the ability of iron-thiolate model complexes to activate O2 is expected to improve the understanding of the key factors that direct reactivity to either iron or sulfur. We report here the structural and redox properties of a thiolate-based dinuclear Fe complex, [FeII2(LS)2] (LS2- = 2,2'-(2,2'-bipyridine-6,6'-iyl)bis(1,1-diphenylethanethiolate)), and its reactivity with dioxygen, in comparison with its previously reported protonated counterpart, [FeII2(LS)(LSH)]+. When reaction with O2 occurs in the absence of protons or in the presence of 1 equiv of proton (i.e., from [FeII2(LS)(LSH)]+), unsupported μ-oxo or μ-hydroxo FeIII dinuclear complexes ([FeIII2(LS)2O] and [FeIII2(LS)2(OH)]+, respectively) are generated. [FeIII2(LS)2O], reported previously but isolated here for the first time from O2 activation, is characterized by single crystal X-ray diffraction and Mössbauer, resonance Raman, and NMR spectroscopies. The addition of protons leads to the release of water and the generation of a mixture of two Fe-based "oxygen-free" species. Density functional theory calculations provide insight into the formation of the μ-oxo or μ-hydroxo FeIII dimers, suggesting that a dinuclear μ-peroxo FeIII intermediate is key to reactivity, and the structure of which changes as a function of protonation state. Compared to previously reported Mn-thiolate analogues, the evolution of the peroxo intermediates to the final products is different and involves a comproportionation vs a dismutation process for the Mn and Fe derivate, respectively.


Determining posture from physiological tremor.
The measurement of body and limb posture is important to many clinical and research studies. Current approaches either directly measure posture (e.g., using optical or magnetic methods) or more indirectly measure it by integrating changes over time (e.g., using gyroscopes and/or accelerometers). Here, we introduce a way of estimating posture from movements without requiring integration over time and the resulting complications. We show how the almost imperceptible tremor of the hand is affected by posture in an intuitive way and therefore can be used to estimate the posture of the arm. We recorded postures and tremor of the arms of volunteers. By using only the minor axis in the covariance of hand tremor, we could estimate the angle of the forearm with a standard deviation of about 4° when the subject's elbow is resting on a table and about 10° when it is off the table. This technique can also be applied as a post hoc analysis on other hand-position data sets to extract posture. This new method allows the estimation of body posture from tremor, is complementary to other techniques, and so can become a useful tool for future research and clinical applications.


Polymyalgia rheumatica--a clinical study with particular reference to arterial disease.
The clinical and laboratory findings in patients with polymyalgia rheumatica are described and reviewed against a background of 59 cases. An increased incidence of the disease in summer and winter was noted. The necessity for a sedimentation rate of 50 mm/1 hour as a diagnostic criteria is questioned and the difficulties in management are discussed. The value of examining the vascular tree is emphasized, since vascular bruits and tenderness may be found which disappear with treatment. Viral antibody studies produced negative results. However, an arterial basis for the disease is confirmed by lymphocyte transformation studies. An hypothesis is suggested that an autoallergic reaction to an antigen in the internal elastic lamina may explain the clinical, biochemical and histological abnormalities.


A deep convolutional neural network for estimating hemodynamic response function with reduction of motion artifacts in fNIRS.
Objective. Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for monitoring hemoglobin concentration changes in a non-invasive manner. However, subject movements are often significant sources of artifacts. While several methods have been developed for suppressing this confounding noise, the conventional techniques have limitations on optimal selections of model parameters across participants or brain regions. To address this shortcoming, we aim to propose a method based on a deep convolutional neural network (CNN).Approach. The U-net is employed as a CNN architecture. Specifically, large-scale training and testing data are generated by combining variants of hemodynamic response function (HRF) with experimental measurements of motion noises. The neural network is then trained to reconstruct hemodynamic response coupled to neuronal activity with a reduction of motion artifacts.Main results. Using extensive analysis, we show that the proposed method estimates the task-related HRF more accurately than the existing methods of wavelet decomposition and autoregressive models. Specifically, the mean squared error and variance of HRF estimates, based on the CNN, are the smallest among all methods considered in this study. These results are more prominent when the semi-simulated data contain variants of shapes and amplitudes of HRF.Significance. The proposed CNN method allows for accurately estimating amplitude and shape of HRF with significant reduction of motion artifacts. This method may have a great potential for monitoring HRF changes in real-life settings that involve excessive motion artifacts.


Association between sex and survival after out-of-hospital cardiac arrest: A systematic review and meta-analysis.
The current literature on sex differences in 30-day survival following out-of-hospital cardiac arrest (OHCA) is conflicting, with 3 recent systematic reviews reporting opposing results. To address these contradictions, this systematic literature review and meta-analysis aimed to synthesize the literature on sex differences in survival after OHCA by including only population-based studies and through separate meta-analyses of crude and adjusted effect estimates. MEDLINE and Embase databases were systematically searched from inception to March 23, 2022 to identify observational studies reporting sex-specific 30-day survival or survival until hospital discharge after OHCA. Two meta-analyses were conducted. The first included unadjusted effect estimates of the association between sex and survival (comparing males vs females), whereas the second included effect estimates adjusted for possible mediating and/or confounding variables. The PROSPERO registration number was CRD42021237887, and the search identified 6712 articles. After the screening, 164 potentially relevant articles were identified, of which 26 were included. The pooled estimate for crude effect estimates (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.22-1.66) indicated that males have a higher chance of survival after OHCA than females. However, the pooled estimate for adjusted effect estimates shows no difference in survival after OHCA between males and females (OR, 0.93; 95% CI, 0.84-1.03). Both meta-analyses involved high statistical heterogeneity between studies: crude pooled estimate I2 = 95.7%, adjusted pooled estimate I2 = 91.3%. There does not appear to be a difference in survival between males and females when effect estimates are adjusted for possible confounding and/or mediating variables in non-selected populations.


Nucleoside reverse transcriptase inhibitors (NRTIs) induce proinflammatory cytokines in the CNS via Wnt5a signaling.
HAART is very effective in suppressing HIV-1 replication in patients. However, patients staying on long-term HAART still develop various HIV-associated neurological disorders, even when the viral load is low. The underlying pathogenic mechanisms are largely unknown. Emerging evidence implicated that persistent neuroinflammation plays an important role in NeuroAIDS. Although residual virus or viral proteins are commonly thought as the causal factors, we are interested in the alternative possibility that HAART critically contributes to the neuroinflammation in the central nervous system (CNS). To test this hypothesis, we have determined the effect of NRTIs on the expression of proinflammatory cytokines in the various CNS regions. Mice (C57Bl/6) were administered with AZT (Zidovudine 100 mg/kg/day), 3TC (Lamivudine 50 mg/kg/day) or D4T (Stavudine 10 mg/kg/day) for 5 days, and cortices, hippocampi and spinal cords were collected for immunoblotting. Our results showed that NRTI administration up-regulated cytokines, including IL-1β, TNF-α and IL-6 in various CNS regions. In addition, we found that NRTIs also up-regulated Wnt5a protein. Importantly, BOX5 attenuated NRTI-induced cytokine up-regulation. These results together suggest that NRTIs up-regulate proinflammatory cytokines via a Wnt5a signaling-dependent mechanism. Our findings may help understand the potential pathogenic mechanisms of HAART-associated NeuroAIDS and design effective adjuvants.


Quantitative review of studies of dietary fat and rat colon carcinoma.
A quantitative overview of 14 studies of rat colon carcinogenesis was undertaken to examine the relationship between fat intake, and fat intake by degree of saturation, on the incidence of colon carcinoma while controlling for calorie consumption. Calorie consumption was not recorded in 11 of the 14 studies. Hence, two types of analyses were conducted. The first examines carcinoma incidence as a function of percent fat (by weight), with calories controlled for by including weight gain per week in the analysis. The second estimates calories per day, for studies not providing such information, using weight gain per week and age at death, followed by a joint analysis of estimated fat calories and estimated total calories. With either approach, a rather strong positive relationship between colon carcinoma incidence and fat intake is indicated for Fischer 344 rats, but no association is apparent for Sprague-Dawley rats. This situation is somewhat clarified when the degree of saturation is taken into account: both strains gave results that suggest a negative relationship between colon cancer incidence and omega-3 fatty acids intake and a positive relationship with non-omega-3 polyunsaturated fat intake among Fischer 344 rats. These analyses suggest an important and specific role for dietary fat in the promotion of rat colon carcinoma.


SOLAR ultraviolet radiation and vitamin D: a historical perspective.
Rickets, the state of vitamin D deficiency, has reemerged as a potential problem in the United States. At the dawn of the 20th century, rickets was pervasive among infants residing in the polluted cities of Europe and the northeastern United States. Important milestones in the history of rickets were the understanding that photosynthesized vitamin D and dietary vitamin D were similar, the discernment of the antirachitic potency of artificial and natural ultraviolet rays, and the discovery that ultraviolet irradiation could render various foods antirachitic. Clinical guidelines were instituted to promote sensible exposure to sunlight and artificial ultraviolet radiation. In addition, irradiated ergosterol from yeast became the major vitamin D source for food fortification and the treatment of rickets, leading to a public health campaign to eradicate rickets by the 1930s. We review the sequence and turn of events pertaining to the discovery of vitamin D and the strategies for the eradication of the reemerging rickets problem.


Human Neuraminidase Isoenzymes Show Variable Activities for 9- O-Acetyl-sialoside Substrates.
Recognition of terminal sialic acids is central to many cellular processes, and structural modification of sialic acid can disrupt these interactions. A prominent, naturally occurring, modification of sialic acid is 9- O-acetylation (9- O-Ac). Study of this modification through generation and analysis of 9- O-Ac sialosides is challenging because of the lability of the acetate group. Fundamental questions regarding the role of 9- O-Ac sialic acids remain unanswered, including what effect it may have on recognition and hydrolysis by the human neuraminidase enzymes (hNEU). To investigate the substrate activity of 9- O-acetylated sialic acids (Neu5,9Ac2), we synthesized an acetylated fluorogenic hNEU substrate 2'-(4-methylumbelliferyl)-9- O-acetyl-α-d- N-acetylneuraminic acid. Additionally, we generated a panel of octyl sialyllactosides containing modified sialic acids including variation in linkage, 9- O-acetylation, and C-5 group (Neu5Gc). Relative rates of substrate cleavage by hNEU were determined using fluorescence spectroscopy and electrospray ionization mass spectrometry. We report that 9- O-acetylation had a significant, and differential, impact on sialic acid hydrolysis by hNEU with general substrate tolerance following the trend of Neu5Ac > Neu5Gc ≫ Neu5,9Ac2 for NEU2, NEU3, and NEU4. Both NEU2 and NEU3 had remarkably reduced activity for Neu5,9Ac2 containing substrates. Other isoenzymes appeared to be more tolerant, with NEU4 even showing increased activity on Neu5,9Ac2 substrates with an aryl aglycone. The impact of these minor structural changes to sialic acid on hNEU activity was unexpected, and these results provide evidence of the substantial influence of 9- O-Ac modifications on hNEU enzyme substrate specificity. Furthermore, these findings may implicate hNEU in processes governed by 9- O-acetyltransferases and -esterases.


Midtrimester genetic amniocentesis in eastern Ontario: a review from 1970 to 1985.
Greater use of genetic amniocentesis in the Eastern Ontario region occurred once the results from the various national trials were published. Acceptance also paralleled an increase in the number of low parity older women having children and the centralisation and greater publicity given to our programme in the late 1970s. A centralised approach has had the positive effects of preventing unnecessary procedures, assuring appropriate patient counselling, follow up, and review, and of increasing obstetric and laboratory expertise. Advanced maternal age has been largely responsible for the increased demand for the service and accounted for an increasing proportion of tests performed, while the absolute number for several other diagnostic categories remained unchanged. We found no evidence that women with a history of previous miscarriage had a higher rate of pregnancy loss following the procedure, and comparison with a group of women who declined amniocentesis did not show that the test increased the risk of miscarriage.


Ontology based document enrichment in bioinformatics.
Controlled vocabularies are common within bioinformatics resources. They can be used to give a summary of the knowledge held about a particular entity. They are also used to constrain values given for particular attributes of an entity. This helps create a shared understanding of a domain and aids increased precision and recall during querying of resources. Ontologies can also provide such facilities, but can also enhance their utility. Controlled vocabularies are often simply lists of words, but may be viewed as a kind of ontology. Ideally ontologies are structurally enriched with relationships between terms within the vocabulary. Use of such rich forms of vocabularies in database annotation could enhance those resources usability by both humans and computers. The representation of the knowledge content of biological resources in a computationally accessible form opens the prospect of greater support for a biologist investigating new data.


Aspartame optical biosensor with bienzyme-immobilized eggshell membrane and oxygen-sensitive optode membrane.
An aspartame optical biosensor has been fabricated by employing a bienzyme system composed of alpha-chymotrypsin and alcohol oxidase immobilized onto an eggshell membrane and an oxygen-sensitive optode membrane as the transducer. The detection schemes involve the enzymatic reactions of aspartame leading to the depletion of the oxygen level of the medium with a concomitant enhancement of the fluorescence intensity of the oxygen-sensitive membrane. The scanning electron and transmission electron micrographs show the microstructure of the eggshell membrane which is successfully immobilized with bienzyme. Using this novel immobilization technique, the aspartame biosensor shows extremely good stability with a shelf life of at least 8 months. The rate change of the fluorescence intensity in 4 min is found to be linearly related to the concentration of aspartame. The useful analytical working range of the biosensor is from 0.056 to 3.07 mM aspartame. The effects of temperature, pH, and ionic strength on the response of the aspartame biosensor are investigated in detail. Citric acid, cyclamic acid, D-fructose, D-galactose, D-glucose, hydrogen peroxide, DL-malic acid, L-phenylalanine, saccharin, sodium benzoate, and sucrose show no interferences but ethanol interferes strongly. The aspartame biosensor has been applied to determine aspartame contents in some commercial products.


A comprehensive dosimetric study on switching from a Type-B to a Type-C dose algorithm for modern lung SBRT.
Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning. Fifty-two lung SBRT patients were included, each planned using coplanar VMAT arcs, normalized to D95% = prescription dose using a Type-B algorithm. These were compared against three Type-C plans: re-calculated plans (identical plan parameters), re-normalized plans (D95% = prescription dose), and re-optimized plans. Dosimetric endpoints were extracted and compared among the four plans, including RTOG dosimetric criteria: (R100%, R50%, D2cm, V105%, and lung V20), PTV Dmin, Dmax, Dmean, V% and D90%, PTV coverage (V100%), homogeneity index (HI), and Paddick conformity index (PCI). Re-calculated Type-C plans resulted in decreased PTV Dmin with a mean difference of 5.2% and increased Dmax with a mean difference of 3.1%, similar or improved RTOG dose compliance, but compromised PTV coverage (mean D95% and V100% reduction of 2.5 and 8.1%, respectively). Seven plans had >5% D95% reduction (maximum reduction = 16.7%), and 18 plans had >5% V100% reduction (maximum reduction = 60.0%). Re-normalized Type-C plans restored target coverage, but yielded degraded plan conformity (average PCI reduction 4.0%), and RTOG dosimetric criteria deviation worsened in 11 plans, in R50%, D2cm, and R100%. Except for one case, re-optimized Type-C plans restored RTOG compliance achieved by the original Type-B plans, resulting in similar dosimetric values but slightly higher target dose heterogeneity (mean HI increase = 13.2%). Type-B SBRT lung plans considerably overestimate target coverage for some patients, necessitating Type-C re-normalization or re-optimization. Current RTOG dosimetric criteria appear to remain appropriate.


Clinical pathway of COVID-19 patients in primary health care in 30 European countries: Eurodata study.
Most COVID-19 patients were treated in primary health care (PHC) in Europe. To demonstrate the scope of PHC workflow during the COVID-19 pandemic emphasising similarities and differences of patient's clinical pathways in Europe. Descriptive, cross-sectional study with data acquired through a semi-structured questionnaire in PHC in 30 European countries, created ad hoc and agreed upon among all researchers who participated in the study. GPs from each country answered the approved questionnaire. Main variable: PHC COVID-19 acute clinical pathway. All variables were collected from each country as of September 2020. COVID-19 clinics in PHC facilities were organised in 8/30. Case detection and testing were performed in PHC in 27/30 countries. RT-PCR and lateral flow tests were performed in PHC in 23/30, free of charge with a medical prescription. Contact tracing was performed mainly by public health authorities. Mandatory isolation ranged from 5 to 14 days. Sick leave certification was given exclusively by GPs in 21/30 countries. Patient hotels or other resources to isolate patients were available in 12/30. Follow-up to monitor the symptoms and/or new complementary tests was made mainly by phone call (27/30). Chest X-ray and phlebotomy were performed in PHC in 18/30 and 23/30 countries, respectively. Oxygen and low-molecular-weight heparin were available in PHC (21/30). In Europe PHC participated in many steps to diagnose, treat and monitor COVID-19 patients. Differences among countries might be addressed at European level for the management of future pandemics.


Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia.
The sentinel and immune functions of microglia require rapid and appropriate reactions to infection and damage. Their Toll-like receptors (TLRs) sense both as threats. However, whether activated microglia mount uniform responses or whether subsets conduct selective tasks is unknown. We demonstrate that murine microglia reorganize their responses to TLR activations postnatally and that this process comes with a maturation of TLR4-organized functions. Although induction of MHCI for antigen presentation remains as a pan-populational feature, synthesis of TNFα becomes restricted to a subset, even within adult central nervous system regions. Response heterogeneity is evident ex vivo, in situ, and in vivo, but is not limited to TNFα production or to TLR-triggered functions. Also, clearance activities for myelin under physiological and pathophysiological conditions, IFNγ-enforced upregulation of MHCII, or challenged inductions of other proinflammatory factors reveal dissimilar microglial contributions. Notably, response heterogeneity is also confirmed in human brain tissue. Our findings suggest that microglia divide by constitutive and inducible capacities. Privileged production of inflammatory mediators assigns a master control to subsets. Sequestration of clearance of endogenous material versus antigen presentation in exclusive compartments can separate potentially interfering functions. Finally, subsets rather than a uniform population of microglia may assemble the reactive phenotypes in responses during infection, injury, and rebuilding, warranting consideration in experimental manipulation and therapeutic strategies.


The efficacy and safety of a Chinese herbal product (Xiao-Feng-San) for the treatment of refractory atopic dermatitis: a randomized, double-blind, placebo-controlled trial.
Severe and widespread atopic dermatitis often fails to respond adequately to topical steroids and oral antihistamines and requires immunomodulatory drugs which, although effective, have undesirable toxic effects. In this prospective, randomized, double-blind, placebo-controlled trial, 71 patients with severe intractable atopic dermatitis were given an 8-week treatment with oral Xiao-Feng-San (XFS; 47 patients) or placebo (24 patients). Total lesion score, erythema score, surface damage score, pruritus score and sleep score were measured at 4-week intervals. Fifty-six patients completed both the treatment and follow-up periods. The decrease in the total lesion score in the treatment group at 8 weeks was significantly greater than that of the placebo group (79.7 ± 5.8% vs. 13.5 ± 7.64%; p < 0.001). There was also a statistically significant difference between the treatment and placebo groups with regard to erythema, surface damage, pruritus and sleep scores. The difference between the 2 groups was still significant for all outcome measures except the erythema score at the 12-week follow-up, 4 weeks after the 8-week treatment had ended. Patients reported no side effects from treatment, although some commented on the unpalatability of the medication. Our study results suggest that the traditional Chinese herbal medicine XFS may be an alternative choice of therapy for severe, refractory, extensive and nonexudative atopic dermatitis.


Consumer advocate and clinician perceptions of consumer participation in two rural mental health services.
Consumer participation has been heralded as the integration of consumer perspectives into standard mental health care. Using a qualitative descriptive method, this study had two broad aims. First, the study aimed to explore the perceptions of consumer advocates and clinicians regarding consumer participation in two new regional mental health services. Second, the study aimed to explore how broad policy initiatives, related to consumer participation, are enacted at a service delivery level. In-depth interviews were conducted with 10 participants, recruited from the steering committees of both services. Although all participants uniformly commended consumer participation as a reality in mental health services, its breadth and depth of influence was not enacted. A systemic change to the way consumer participation is funded and incorporated into mental health services is required. The incorporation of consumers as stakeholders within mental health services requires commitment to the idea, the establishment of clear purposes and roles, and commensurate funding to enable consumers to be stakeholders with similar resources to other stakeholder groups.


Myocardial systolic and diastolic consequences of left ventricular mechanical dyssynchrony in heart failure with normal left ventricular ejection fraction.
The purpose of this study was to test the hypothesis that left ventricular (LV) mechanical dyssynchrony deteriorates the longitudinal systolic and diastolic function of the left ventricle (LV) in patients with heart failure with a normal LV ejection fraction (HFNEF). In patients with HFNEF and in a control group consisting of asymptomatic patients with LV diastolic dysfunction [LVDD], matched by age, gender, and LV ejection fraction, we assessed the global longitudinal systolic (global strain), diastolic [global early-diastolic strain rate (SRe)], and synchronous (standard deviation of time-to-peak systolic strain) function of the LV by two-dimensional speckle-tracking echocardiography using a 18-segment LV model. A total of 325 patients were included (85 with HFNEF and 240 with asymptomatic LVDD). Patients with HFNEF had a significant impairment of the longitudinal systolic and diastolic function of the LV as compared with the control group. Concerning the pathophysiological mechanisms linked to these findings, we found that HFNEF patients with asynchronous LV contractions had significantly more impaired longitudinal systolic and diastolic LV function (global strain -14.76 ± 3.44%, global SRe 0.79 ± 0.24 s(-1)) than patients without asynchronous LV contractions (global strain -18.57 ± 3.10%, global SRe 1.06 ± 0.32 s(-1); all P < 0.0001). Accordingly, in HFNEF patients with LV mechanical dyssynchrony the rates of LV longitudinal systolic and diastolic dysfunction were 64 and 70%, respectively, whereas these rates were significantly lower (19.5 and 41.3%), respectively, in patients without asynchronous LV contractions. In addition, HFNEF patients with LV mechanical dyssynchrony presented higher LV filling pressures and worse NYHA functional class than those with normal LV contractions. In patients with HFNEF, LV mechanical dyssynchrony is associated with an important impairment of the longitudinal systolic and diastolic function of the LV. Therefore, the restoration of asynchronous LV contractions could help to improve and/or correct both the systolic and the diastolic longitudinal dysfunction of the LV in HFNEF and thereby improve the symptomatology of these patients.


Coparenting, mother-infant interaction, and infant-parent attachment relationships in two-parent families.
Coparenting behavior and the quality of mothers' parenting behavior were examined in relation to parents' perceptions of their child's attachment in 60 two-parent families with 11- to 15-month-old infants (30 boys and 30 girls). Parent-child attachment was assessed using the Attachment Q-Sort. Competitive coparenting was associated with mothers' and fathers' perception of a less secure parent-child attachment relationship, whereas maternal responsiveness was associated with mothers' perception of a more secure mother-child attachment relationship. Families with mothers who were more restrictive and those with parents who were more competitive were less likely to have mothers and fathers with similar perceptions of the quality of parent-child attachment relationships. Findings support the proposal that different levels of family functioning affect the quality of parent-child relationships.


Transforming Palmyra Atoll to native-tree dominance will increase net carbon storage and reduce dissolved organic carbon reef runoff.
Native forests on tropical islands have been displaced by non-native species, leading to calls for their transformation. Simultaneously, there is increasing recognition that tropical forests can help sequester carbon that would otherwise enter the atmosphere. However, it is unclear if native forests sequester more or less carbon than human-altered landscapes. At Palmyra Atoll, efforts are underway to transform the rainforest composition from coconut palm (Cocos nucifera) dominated to native mixed-species. To better understand how this landscape-level change will alter the atoll's carbon dynamics, we used field sampling, remote sensing, and parameter estimates from the literature to model the total carbon accumulation potential of Palmyra's forest before and after transformation. The model predicted that replacing the C. nucifera plantation with native species would reduce aboveground biomass from 692.6 to 433.3 Mg C. However, expansion of the native Pisonia grandis and Heliotropium foertherianum forest community projected an increase in soil carbon to at least 13,590.8 Mg C, thereby increasing the atoll's overall terrestrial carbon storage potential by 11.6%. Nearshore sites adjacent to C. nucifera canopy had a higher dissolved organic carbon (DOC) concentration (110.0 μMC) than sites adjacent to native forest (81.5 μMC), suggesting that, in conjunction with an increase in terrestrial carbon storage, replacing C. nucifera with native forest will reduce the DOC exported from the forest into in nearshore marine habitats. Lower DOC levels have potential benefits for corals and coral dependent communities. For tropical islands like Palmyra, reverting from C. nucifera dominance to native tree dominance could buffer projected climate change impacts by increasing carbon storage and reducing coral disease.


Parental educational level and injury incidence and mortality among foreign-born children: a cohort study with 46 years follow-up.
Injury risk during childhood and adolescence vary depending on socio-economic factors. The aim of this study was to study if the risk of fatal and non-fatal unintentional injuries among foreign-born children was similar across parental educational level or not. In this retrospective cohort study we followed 907,335 children between 1961 and 2007 in Sweden. We established the cohort by linkage between Swedish national registers including cause of death register and in-patient register, through unique Personal Identification Numbers. The main exposure variable was parental (maternal and paternal) educational level. The cohorts was followed from start date of follow-up period, or date of birth whichever occurred last, until exit date from the cohort, which was date of hospitalization or death due to unintentional injury, first emigration, death due to other causes than injury or end of follow-up, whichever came first. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) by Cox proportional hazards regression models. Overall, we found 705 and 78,182 cases of death and hospitalization due to unintentional injuries, respectively. Risk of death and hospitalization due to unintentional injuries was statistically significantly 1.48 (95% CI: 1.24-1.78) and 1.10 (95% CI: 1.08-1.12) times higher among children with lowest parental educational level (9 years and shorter years of study) compared to children with highest parental educational level (+13 years of study). We found similar results when stratified our study group by sex of children, by maternal and paternal educational level separately, and injury type (traffic-related, fall, poisoning, burn and drowning). It seems injury prevention work against unintentional injuries is less effective among children with low parental education compared with those with higher parental education. We recommend designing specific preventive interventions aiming at children with low parental education.


Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage.
The separation of sister chromatids in anaphase is followed by spindle disassembly and cytokinesis. These events are governed by the anaphase-promoting complex (APC), which triggers the ubiquitin-dependent proteolysis of key regulatory proteins: anaphase requires the destruction of the anaphase inhibitor Pds1, whereas mitotic exit requires the destruction of mitotic cyclins and the inactivation of Cdk1. We find that Pds1 is not only an inhibitor of anaphase, but also blocks cyclin destruction and mitotic exit by a mechanism independent of its effects on sister chromatid separation. Pds1 is also required for the mitotic arrest and inhibition of cyclin destruction that occurs after DNA damage. Even in anaphase cells, where Pds1 levels are normally low, DNA damage stabilizes Pds1 and prevents cyclin destruction and mitotic exit. Pds1 blocks cyclin destruction by inhibiting its binding partner Esp1. Mutations in ESP1 delay cyclin destruction; overexpression of ESP1 causes premature cyclin destruction in cells arrested in metaphase by spindle defects and in cells arrested in metaphase and anaphase by DNA damage. The effects of Esp1 are dependent on Cdc20 (an activating subunit of the APC) and on several additional proteins (Cdc5, Cdc14, Cdc15, Tem1) that form a regulatory network governing mitotic exit. We speculate that the inhibition of cyclin destruction by Pds1 may contribute to the ordering of late mitotic events by ensuring that mitotic exit is delayed until after anaphase is initiated. In addition, the stabilization of Pds1 after DNA damage provides a mechanism to delay both anaphase and mitotic exit while DNA repair occurs.


Bilophila wadsworthia isolated from clinical specimens in Taiwan.
Bilophila wadsworthia, a newly discovered anaerobic gram-negative species, has been found in such various clinical specimens as bile, pus, blood et cetera, in addition to appendicitis specimens. The formation of black center colonies in bacteroides bile esculin (BBE) agar is one of the important characteristics of the species.


The incidence of adenocarcinoma and squamous cell carcinoma of the esophagus: Barrett's esophagus makes a difference.
Adenocarcinoma limited to the esophagus (ACE) arises in Barrett's esophagus (BE). The incidence of ACE is therefore restricted to this BE subpopulation, whose size is unknown and which is for 95% unidentified. To determine the age- and gender-specific incidence rates of ACE, limited to the BE subpopulation, within a defined geographical area and to compare them with those of squamous cell carcinoma of the esophagus (SCC), which can affect the entire population. The age- and gender-specific incidence rates for ACE and adenocarcinoma of the cardia (AGC) were calculated after an expert panel classified 87% of all cases of adenocarcinoma of the esophagus reported to the Danish Cancer Registry over a 6-yr period as ACE or AGC. The age-specific incidence rates of ACE for males rose from 0.09/10(5) (30-34 yr) to 14.14/10(5) (80-84 yr), falling to 7.2/10(5) (85+ yr), for females from 0.19/10(5) (45-49 yr) to 2.79/10(5) (80-84 yr), falling to 2.43/10(5) (85+ yr) and yielding a gender ratio of 5.9:1; AGC demonstrated a similar pattern and a gender ratio of 4.26:1. However, the incidence rates of SCC continued rising after the age of 80 yr, with a gender ratio of 2.46:1. The continuing rise in the SCC incidence rates in the elderly demonstrated that the unexpected decline and fall in the incidence rates of ACE over the age of 80 yr did not result from underdiagnosis but were most probably caused by a declining prevalence rate of BE, restricting the elderly BE subpopulation at risk of developing ACE.


Infection Prevention Practices in Japan, Thailand, and the United States: Results From National Surveys.
Numerous evidence-based practices for preventing device-associated infections are available, yet the extent to which these practices are regularly used in acute care hospitals across different countries has not been compared, to our knowledge. Data from hospital surveys conducted in Japan, the United States, and Thailand in 2012, 2013, and 2014, respectively, were evaluated to determine the use of recommended practices to prevent central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection (CAUTI). The outcomes were the percentage of hospitals reporting regular use (a score of 4 or 5 on a scale from 1 [never use] to 5 [always use]) of each practice across countries and identified hospital characteristics associated with the use of selected practices in each country. Survey response rates were 71% in Japan and the United States and 87% in Thailand. A majority of hospitals in Japan (76.6%), Thailand (63.2%), and the United States (97.8%) used maximum barrier precautions for preventing CLABSI and semirecumbent positioning to prevent VAP (66.2% for Japan, 86.7% for Thailand, and 98.7% for the United States). Nearly all hospitals (>90%) in Thailand and the United States reported monitoring CLABSI, VAP, and CAUTI rates, whereas in Japan only CLABSI rates were monitored by a majority of hospitals. Regular use of CAUTI prevention practices was variable across the 3 countries, with only a few practices adopted by >50% of hospitals. A majority of hospitals in Japan, Thailand, and the United States have adopted certain practices to prevent CLABSI and VAP. Opportunities for targeting prevention activities and reducing device-associated infection risk in hospitals exist across all 3 countries.


Healthy Universities. The development and implementation of a holistic health promotion intervention programme especially adapted for staff working in the higher educational sector: the ARK study.
Underpinned by the Healthy Universities settings concept, this paper presents a holistic intervention approach, called ARK, to improve the health and well-being of academic staff. ARK (a Norwegian acronym for work environment and climate study) has been conducted in 18 universities and university colleges in Norway. The survey has collected information on employees' perceptions of the psychosocial work environment, well-being, and health from over 15,000 respondents. Further, it has provided valuable information and experiences on organizational development processes on how to successfully implement a health-promoting intervention programme. The aim of this paper is to present the ARK project and provide suggestions on how to conduct a health-promoting intervention programme in a university setting based on the experience and knowledge acquired from ARK. This understanding can inform and inspire the planning of future Health Promoting University initiatives to meet the distinctive needs of its employees.