Exploration of Chemical Diversity in Intercellular Quorum Sensing Signalling Systems in Prokaryotes.
Quorum sensing (QS) serves as a vital means of intercellular signalling in a variety of prokaryotes, which enables single cells to act in multicellular configurations. The potential to control community-wide responses has also sparked numerous recent biotechnological innovations. However, our capacity to utilize intercellular communication is hindered due to a scarcity of complementary signalling systems and a restricted comprehension of interconnections between these systems caused by variations in their dynamic range. In this study, we utilize uniform manifold approximation and projection and extended-connectivity fingerprints to explore the available chemical space of QS signalling molecules. We investigate and experimentally characterize a set of closely related QS signalling ligands, consisting of N-acyl homoserine lactones and the aryl homoserine lactone p-coumaroyl, as well as a set of more widely diverging QS ligands, consisting of photopyrones, dialkylresorcinols, 3,5-dimethylpyrazin-2-ol and autoinducer-2, and define their performance. We report on a set of six signal- and promoter-orthogonal intercellular QS signalling systems, significantly expanding the toolkit for engineering community-wide behaviour. Furthermore, we demonstrate that ligand diversity can serve as a statistically significant tool to predict much more complicated ligand-receptor interactions. This approach highlights the potential of dimensionality reduction to explore chemical diversity in microbial dynamics.


Optimal experimental design for sampling voltage on dendritic trees in the low-SNR regime.
Due to the limitations of current voltage sensing techniques, optimal filtering of noisy, undersampled voltage signals on dendritic trees is a key problem in computational cellular neuroscience. These limitations lead to voltage data that is incomplete (in the sense of only capturing a small portion of the full spatiotemporal signal) and often highly noisy. In this paper we use a Kalman filtering framework to develop optimal experimental design methods for voltage sampling. Our approach is to use a simple greedy algorithm with lazy evaluation to minimize the expected square error of the estimated spatiotemporal voltage signal. We take advantage of some particular features of the dendritic filtering problem to efficiently calculate the Kalman estimator's covariance. We test our framework with simulations of real dendritic branching structures and compare the quality of both time-invariant and time-varying sampling schemes. While the benefit of using the experimental design methods was modest in the time-invariant case, improvements of 25-100% over more naïve methods were found when the observation locations were allowed to change with time. We also present a heuristic approximation to the greedy algorithm that is an order of magnitude faster while still providing comparable results.


Population and evolutionary dynamics of Shiga-toxin producing Escherichia coli O157 in a beef herd: A longitudinal study.
Shiga toxin producing Escherichia coli O157:H7 (STEC O157) is naturally found in the gastrointestinal tract of cattle and can cause severe disease in humans. There is limited understanding of the population dynamics and microevolution of STEC O157 at herd level. In this study, isolates from a closed beef herd of 23 cows were used to examine the population turnover in the herd. Of the nine STEC O157 clades previously described, clade 7 was found in 162 of the 169 isolates typed. Multiple locus variable number tandem repeat analysis (MLVA) differentiated 169 isolates into 33 unique MLVA types. Five predominant MLVA types were evident with most of the remaining types containing only a single isolate. MLVA data suggest that over time clonal replacement occurred within the herd. Genome sequencing of 18 selected isolates found that the isolates were divided into four lineages, representing four different 'clones' in the herd. Genome data confirmed clonal replacement over time and provided evidence of cross transmission of strains between cows. The findings enhanced our understanding of the population dynamics of STEC O157 in its natural host that will help developing effective control measures to prevent the spread of the pathogen to the human population.


Distinguishing bipolar from unipolar depression: the importance of clinical symptoms and illness features.
Distinguishing bipolar disorder (BP) from major depressive disorder (MDD) has important relevance for prognosis and treatment. Prior studies have identified clinical features that differ between these two diseases but have been limited by heterogeneity and lack of replication. We sought to identify depression-related features that distinguish BP from MDD in large samples with replication. Using a large, opportunistically ascertained collection of subjects with BP and MDD we selected 34 depression-related clinical features to test across the diagnostic categories in an initial discovery dataset consisting of 1228 subjects (386 BPI, 158 BPII and 684 MDD). Features significantly associated with BP were tested in an independent sample of 1000 BPI cases and 1000 MDD cases for classifying ability in receiver operating characteristic (ROC) analysis. Seven clinical features showed significant association with BPI compared with MDD: delusions, psychomotor retardation, incapacitation, greater number of mixed symptoms, greater number of episodes, shorter episode length, and a history of experiencing a high after depression treatment. ROC analyses of a model including these seven factors showed significant evidence for discrimination between BPI and MDD in an independent dataset (area under the curve = 0.83). Only two features (number of mixed symptoms, and feeling high after an antidepressant) showed an association with BPII versus MDD. Our study suggests that clinical features distinguishing depression in BPI versus MDD have important classification potential for clinical practice, and should also be incorporated as 'baseline' features in the evaluation of novel diagnostic biomarkers.


Kyphoscoliotic type of Ehlers-Danlos Syndrome (EDS VIA) in six Egyptian patients presenting with a homogeneous clinical phenotype.
The kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VIA) is a rare recessively inherited connective tissue disorder characterized by bruisable, hyperextensible skin, generalized joint laxity, severe muscular hypotonia at birth and progressive congenital scoliosis or kyphosis. Deficiency of the enzyme lysyl hydroxylase 1 (LH1) due to mutations in PLOD1 results in underhydroxylation of collagen lysyl residues and, hence, in the abnormal formation of collagen cross-links. Here, we report on the clinical, biochemical, and molecular findings in six Egyptian patients from four unrelated families severely affected with EDS VIA. In addition to the frequently reported p.Glu326_Lys585dup, we identified two novel sequence variants p.Gln208* and p.Tyr675*, which lead either to loss of function of LH1 or to its deficiency. All affected children presented with similar clinical features of the disorder, and in addition, several dysmorphic craniofacial features, not yet described in EDS VIA. These were specific for the affected individuals of each family, but absent in their parents and their unaffected siblings. Our description of six patients presenting with a homogeneous clinical phenotype and dysmorphic craniofacial features will help pediatricians in the diagnosis of this rare disorder.


Anticancer Organometallic Osmium(II)-p-cymene Complexes.
Osmium compounds are attracting increasing attention as potential anticancer drugs. In this context, a series of bifunctional organometallic osmium(II)-p-cymene complexes functionalized with alkyl or perfluoroalkyl groups were prepared and screened for their antiproliferative activity. Three compounds from the series display selectivity toward cancer cells, with moderate cytotoxicity observed against human ovarian carcinoma (A2780) cells, whereas no cytotoxicity was observed on non-cancerous human embryonic kidney (HEK-293) cells and human endothelial (ECRF24) cells. Two of these three cancer-cell-selective compounds induce cell death largely via apoptosis and were also found to disrupt vascularization in the chicken embryo chorioallantoic membrane (CAM) model. Based on these promising properties, these compounds have potential clinical applications.


Small bowel infarction by Aspergillus.
Primary gut involvement by Aspergillus is a rare and often fatal complication of intensive antileukemic therapy. We describe the case of an adult patient affected by acute leukemia who developed a small bowel fungal thromboembolism without radiographic evidence of lung involvement during the post-induction aplastic phase. The diagnosis was made histologically at laparotomy performed for small bowel perforation. The patient died a week later in spite of amphotericin-B treatment and neutrophil recovery. Anti-Aspergillus prophylaxis and early introduction of amphotericin-B in the treatment of febrile neutropenia is probably advisable in all cases of AML.


Oral misoprostol for induction of labour.
Misoprostol is a synthetic prostaglandin which has been used to induce labour. Oral use of the drug misoprostol may be convenient, but an overdose could cause uterine hyperstimulation and precipitate labour which may be life-threatening for both mother and fetus. The objective of this review was to assess the effects of oral misoprostol used for labour induction in women with a viable fetus. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched in May 2000. Randomised trials of oral misoprostol versus other methods, placebo or no treatment given to women with a viable fetus for labour induction. This is one of a series of the Cochrane reviews of methods of cervical ripening and labour induction using standardised methodology. The Cochrane Pregnancy and Childbirth Group has developed a strategy to deal with the large volume and complexity of trial data related to labour induction. Data from all relevant trials are extracted centrally. They are incorporated into a series of primary reviews arranged by methods of induction of labour. The data from the primary reviews will be incorporated into secondary reviews. The secondary reviews are arranged by category of woman according to parity, membrane status and previous caesarean section. To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific, hierarchical order. This review includes comparisons between oral misoprostol with only those methods above it on the list (placebo, vaginal prostaglandins, intracervical prostaglandins, oxytocin, amniotomy, oxytocin and amniotomy or vaginal misoprostol). One trial with 80 randomised women with prelabour rupture of membranes at term showed that, compared with placebo, oral misoprostol reduces the need for oxytocin infusion from 51 percent to 13 percent (relative risk 0.25, 95% confidence interval 0.1 to 0.6) and shortens delivery time by 8.7 hours (95% CI 6.0 to 11.3). Compared with vaginal prostaglandins, oral misoprostol showed no beneficial or harmful effects. However, only two trials were included with 957 randomised women in total. In six trials with 1042 randomised women that compared oral with vaginal misoprostol, oral misoprostol appeared to be less effective. More women in the oral misoprostol group did not achieve vaginal delivery within 24 hours of randomisation (54.2%) compared with 35.2% in the vaginal misoprostol group (relative risk 1.55, 95% confidence intervals 1.30 to 1.85). Caesarean section rate was 17.7% in the oral misoprostol group compared with 21.7% in the vaginal misoprostol group (relative risk 0.82, 95% confidence intervals 0.64 to 1.05). There was no difference in uterine hyperstimulation with fetal heart rate changes (9.5% versus 9.9%; relative risk 0.93, 95% confidence intervals 0.66 to 1.33). There were no reported cases of severe neonatal and maternal morbidity. Oral misoprostol may be an effective method for labour induction. However, the data on safety are lacking. It is possible that clinically effective oral regimens may have an unacceptably high incidence of complications such as uterine hyperstimulation and possibly uterine rupture.


The presence of novel amino acids in the cytoplasmic domain of stem cell factor results in hematopoietic defects in Steel(17H) mice.
Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF(248)) or membrane-associated (MA) (SCF(220)) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie (Sl(d)) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms. Steel(17H) (Sl(17H)) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl(17H) allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa's) in the SCF cytoplasmic domain with 28 novel aa's. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl(17H)-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl(17H) mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl(17H) isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCF(X9/D3)) SCF in Sl/Sl(17H) mutants results in a significant improvement in peripheral red blood cell counts in comparison to Sl/Sl(17H) mice.


Community reentry: Racial/ethnic differences in unmet needs among adults with co-occurring opioid use and mental health disorder.
Adults with co-occurring opioid use and mental health disorder (COD) recently released from incarceration have many social and health needs that place them at the most significant risk for overdose and poor reentry outcomes. Little is known about racial/ethnic differences in this population. To examine racial/ethnic differences in social and health needs, data were analyzed for 293 adults with COD within two weeks of release, a high-risk period for overdose, from six Massachusetts jails. Overall, participants (62.6% non-Hispanic White, 23.1% Hispanic, 14.3% non-Hispanic Black, and 73.5% male) reported multiple health and social needs across groups. Chi-square tests and Kruskal-Wallis one-way ANOVAs were used to compare social and health needs among racial/ethnic groups. Non-Hispanic Black participants reported more problems with crack/cocaine, whereas Non-Hispanic White and Hispanic participants reported more problems with opioids (p < .001). Despite similar lifetime rates of illicit substance use, non-Hispanic Black and Hispanic participants received less treatment (p < .001). Non-Hispanic White participants reported more opioid and alcohol use (p < .006), trauma symptoms (p = .020), utilization of behavioral health treatment (p = .008), and more medical needs than Hispanic and/or non-Hispanic Black participants (p = .001). Non-Hispanic Black and Hispanic participants reported more needs related to social determinants of health (p = .008). While re-entry is a vulnerable period for all adults with COD, this paper identifies specific needs by race/ethnicity and proposes strategies to advance equity and improve care for all formerly incarcerated adults with a COD.


Coupled Dynamics of Droplet Impact on a Flexible, Hydrophilic Cantilever Beam.
We experimentally study the droplet impact on a flexible, hydrophilic cantilever beam. Droplets of water, water-glycerol (1:1 v/v), and glycerol were considered on a copper beam. Side visualization of the droplet impact on the cantilever was carried out by using a high-speed camera. We systematically vary cantilever stiffness to obtain a characteristic time scale of the beam dynamics, that is, shorter on the same order and longer than the characteristic time scale of droplet dynamics. Water droplet spreading reduces with an increase in the beam's flexibility, due to the "springboard effect". Results reveal that a threshold cantilever length exists beyond which the droplet vibration mode "locks-in" to the cantilever vibration mode. During lock-in, the bending energy of the beam increases with an increasing length or decreasing stiffness. The time-varying cantilever deflection exhibits an oscillatory, exponentially decaying response. However, in the case where both time scales are almost the same, we found a two-stage damping in the measurements: a fast, initial damping followed by a slower, damped response. We explain this damped response by the interplay of droplet and cantilever early dynamics. As expected, increasing the droplet viscosity dampens the magnitude of droplet spreading and displacement of the cantilever's tip due to a larger dissipation of kinetic energy in the bulk of the droplet. The decay is exponential in all cases, and the time taken to reduce the spreading and displacement is shorter with a larger viscosity. The damping coefficient is found to inversely scale with the cantilever length or mass. We corroborated the measurements with available analytical models, confirming the hypotheses used to explain the results. Overall, the present study provides fundamental insights into controlling the coupled dynamics of droplet and flexible substrates, with potential applications such as the design of efficient agricultural sprays and wings of microaerial vehicles.


Molecular cloning, sequencing and functional expression of porcine thyrotropin (TSH) receptor cDNA1).
We directly sequenced PCR fragments amplified from a porcine thyroid cDNA library with various synthetic primers based on the nucleotide sequence of bovine thyrotropin receptor (bTSHR) cDNA. A nucleotide sequence of 2410 bp was determined and its deduced amino acid sequence contained an open reading frame coding 764 amino acids, which showed 91.8% and 89.5% similarity to bTSHR and human TSH receptor, respectively. A hydrophobicity plot of the porcine protein suggested that it had a putative signal peptide and seven transmembrane domains. Chinese hamster ovary cells stably transfected with the cDNA could be specifically bound to bovine TSH (bTSH) and increased the intracellular cAMP level in response to bTSH and Graves' disease patients' sera stimulation.


Student award for outstanding research winner in the Ph.D. category for the 9th World Biomaterials Congress, Chengdu, China, June 1-5, 2012: synthesis and application of photodegradable microspheres for spatiotemporal control of protein delivery.
In this study, the authors present a photodegradable microparticle system that can be used to entrap and deliver bioactive proteins to cells during culture. By using a photosensitive delivery system, experimenters can achieve a wide variety of spatiotemporally regulated release profiles with a single microparticle formulation, thereby, enabling one to probe many questions as to how protein presentation can be manipulated to regulate cell function. Photodegradable microparticles were synthesized via inverse suspension polymerization with a mean diameter of 22 μm, and degradation was demonstrated upon exposure to several irradiation conditions. The protein-loaded depots were incorporated into cell cultures and release of bioactive protein was quantified during the photodegradation process. This phototriggered release allowed for the delivery of TGF-β1 to stimulate PE25 cells and for the delivery of fluorescently labeled Annexin V to assay apoptotic 3T3 fibroblasts during culture. By incorporating these photoresponsive protein delivery depots into cell culture, new types of experiments are now possible to test hypotheses about how individual or multiple soluble factors might affect cell function when presented in a uniform, temporally varying, or gradient manner.


[Experiences with the alloplastic joint prosthesis of the interphalangeal joint].
The replacement of finger joints, especially of the proximal interphalangeal joint (PIP), remains an unsolved problem. Long-term results of conventional reconstructive procedures as well as previously available artificial joint implants have been disappointing. In a controlled study, 12 PIP-joints were replaced by a new type of total endoprosthesis as an alternative to joint fusion. The cementless prosthesis is unhinged and consists of metal joint surfaces. After a follow-up of 18 months, implantation of this metal prosthesis resulted in almost complete pain relief and an active range of movement of 58 degrees. The absolute gain in mobility, however, was only 6 degrees. A swan-neck deformity was found in nine out of 12 cases but corrective surgery was not required. The proximal half of the implant had to be exchanged in two cases due to loosening. All patients were satisfied with the result. The disparity between subjective acceptance by the patients, who clearly prefer joint replacement to fusion, and objective results demonstrates the necessity for further development in this field. The type of prosthesis used in this study seems to be a useful baseline tool which could be turned into a ingenious PIP-joint replacement by further development aiming at reduced abrasion, increased initial stability, a more individual configuration, to name just a few goals.


Direct comparison of an automated oscillometric device with an electronic auscultatory device for epidemiologic survey to evaluate the prevalence of hypertension.
Mercury-free sphygmomanometers are gradually replacing the traditional sphygmomanometers in clinical settings and epidemiological surveys for measuring blood pressure (BP) due to mercury toxicity. No direct comparative studies have evaluated BP differences and statistical errors of automated oscillometric devices (ODs) against electronic auscultatory devices (ADs) for epidemiologic surveys. Herein, we evaluated the validity of ODs for the Korea National Health and Nutrition Examination Survey (KNHANES) using the Universal Standard for BP device validation through a direct comparison with ADs as the reference standard. Four trained observers performed validation on 278 volunteers aged ≥ 19 years with a standardized BP measurement protocol. Agreement between the BP measurements recorded with an OD against those recorded with an AD was assessed by Lin's concordance correlation coefficient (CCC) and Bland-Altman's limits of agreement. To evaluate the agreement for BP classification, weighted kappa values were estimated. To explore the factors associated with BP measurement differences between the 2 devices, multiple linear regression analysis was performed. The average BP differences (OD-AD) were 2.6 ± 6.2 mm Hg for systolic BP (SBP) and -5.1 ± 5.6 mm Hg for diastolic BP (DBP). Lin's CCCs were 0.927 and 0.768 for the overall SBP and DBP, respectively. The cumulative percentage of absolute errors ≤10 mm Hg was 88.1% for SBP and 81.3% for DBP. The weighted kappa value for the Joint National Committee 7 BP classification was 0.75 (95% confidence interval: 0.68-0.81). An OD overestimated the prevalence of SBP (0.3%, P = .0222) and underestimated the prevalence of DBP (1.8%, P < .0001). Multivariate analysis to identify the risk factors for BP difference revealed the arm circumference (AC) to be negatively associated with BP difference. Male sex was positively associated, while age was negatively associated with SBP difference. OD-DBP was positively associated with DBP difference and negatively associated for DBP absolute error. ODs met the accuracy requirements of the Universal Standard criteria against ADs for SBP but not for DBP. Thus, the DBP values may be underestimated by ODs in the KNHANES.


CD147 as a key mediator of the spleen inflammatory response in mice after focal cerebral ischemia.
The splenic inflammatory response after cerebral ischemia has been implicated in secondary brain injury. We have recently reported that CD147 plays an important role in driving brain inflammation after ischemic stroke. In this study, we hypothesized that CD147 may play a role in the splenic inflammatory response after cerebral ischemia. Transient (60 min) middle cerebral artery occlusion was induced in wild-type mice treated with an anti-CD147 antibody (αCD147) 1 h before ischemia onset. The splenic inflammatory response was evaluated at 4 and 24 h, representing the peak and early stage of splenic inflammatory activation in this model. Changes in mRNA and protein expression of CD147 and inflammatory markers were measured using RT-qPCR and western blot, respectively. Immune cells in the spleen and brain were measured using flow cytometry. CD147 expression was rapidly upregulated in the spleen at 4 and 24 h after ischemia onset. The splenic inflammatory response induced by cerebral ischemia was inhibited by αCD147 treatment as demonstrated by the reduced expression of cytokines (TNFα, IL-6, IL-1β) and monocyte chemoattractant protein-1 (MCP-1) in the spleen at 4 and 24 h after ischemia onset. Furthermore, reduced expression of Ly-6C and CCR2 coincided with a decrease in the number of Ly-6Chigh MMs subset in the spleen at 4 h after ischemia onset. This suggests αCD147 treatment abrogates cerebral ischemia-induced inflammatory activation of splenic monocytes/macrophages (MMs). In addition, the experiment in splenectomized mice showed the spleen as the major source of infiltrated Ly-6Chigh MMs subset in the ischemic brain and that brain infiltration of Ly-6Chigh MMs was reduced by αCD147 treatment. These results reveal CD147 as a key mediator of the spleen's inflammatory activation in response to cerebral ischemia.


[Intraoperative conversion and postoperative complication of video-assisted thoracoscopic surgery lobectomy for primary lung cancer].
By 2002, we had attempted video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy for 140 primary lung cancer cases. Four cases (2.9%) were converted to standard posterolateral thoracotomy for oncologic reasons and aortic injury, and 7 cases (5%) were converted to minithoracotomy with a 10 cm incision due to almost injuring the vascular system. Average blood loss in these cases was 379 ml, and there was no blood transfusion required. Seven of these 11 cases had true pleural symphysis in the thoracic cavity. The remaining 129 cases, consisted of 93 lobectomies and 34 segmentectomies, performed with a minithoracotomy of 5 cm using 2 ports. Average surgical duration was 227 minutes, and blood loss was 100 ml. Postoperative complication occurred in 15 patients (11.6%). Major complications included 1 broncho-pleural fistula, 1 pulmonary infarction, 1 cerebral infarction and 1 respiratory failure needed for mechanical ventilation. However, there were no hospital deaths. The mean postoperative hospital stay was 12 days. We recommend that surgeons should pay attention to hilar dissection, particularly in the presences of adhesion and carefully judge whether to convert to thoracotomy at the time of hemorrhage. The VATS procedure has a low mortality and morbidity for lung cancer, but particulaly in high risk patients, requires care and management the same as an open thoracotomy.


Treatment of sound errors in aphasia and apraxia of speech: Effects of phonological complexity.
BACKGROUND: Recent research suggests that the complexity of treatment stimuli influences the effectiveness of treatment. However, no studies have examined the role of complexity on sound production treatment in adult individuals with sound production impairments. AIMS: This study examines effects of syllable complexity on treatment outcome in two patients with acquired sound production problems. Complexity is defined in terms of syllable structure: clusters are more complex than singletons. Using a single-subject multiple-baseline design, we address the question: Is treatment of complex syllables more effective than treatment of simple syllables? METHODS #ENTITYSTARTX00026; PROCEDURES: Two patients with aphasia and apraxia of speech were trained to produce complex or simple syllables (using modelling). Improvement was measured by percent correct on a word and nonword repetition test. OUTCOMES #ENTITYSTARTX00026; RESULTS: We found that both treatment on simple syllables and treatment on complex syllables led to improved production of simple syllables, while treatment of complex syllables also led to improvement on some complex syllables for one of the two patients. CONCLUSIONS: These results suggests that training complex items is more effective than training simple items, at least for some patients. Possible reasons for lack of stronger effects are discussed, as well as directions for future research.


Vitamin D deficiency and associated factors in hemodialysis patients.
Vitamin D deficiency is prevalent in the general elderly population, and is related to an increased risk of osteoporosis, fractures, and cardiovascular calcification. Only limited data and no guidelines are available on vitamin D deficiency in hemodialysis patients. We aimed to assess the frequency of, and factors associated with, 25(OH) vitamin D deficiency in hemodialysis patients in a French dialysis center. In March 2006, we studied all prevalent hemodialysis patients who had not received native vitamin D supplements in the recent past. According to the Kidney Disease Outcomes and Quality Initiative guidelines, patients were assigned to the following 3 groups: group 1, with a sufficient vitamin D serum level (>75 nmol/L); group 2, with an insufficient level (25 to 75 nmol/L); and group 3, with severe deficiency (<25 nmol/L). Patients' characteristics and biochemical findings were compared between patients of groups 1 and 3. Of 253 patients, 11% patients were in group 1; 47% were in group 2; and 42% were in group 3. The proportions of female and diabetes patients were 42% and 34%, respectively. The mean (+/- SD) age of all patients was 66.7 +/- 14 years, and the mean duration of dialysis was 62 +/- 74 months, with a mean schedule of 3 x 6.5 hours and administration of a 1.5 mmol/L calcium dialysate. Concomitant treatment included alfacalcidol (66% of patients) and sevelamer (34% of patients) as a standard phosphate binder. Group 3 patients had a lower dialysis vintage (53 +/- 66 vs. 73 +/- 85 months, P < .05), a higher number of diabetes patients (45% vs. 21%, P < .05), a higher number of female patients (53% vs. 28%, P < .05), and a higher level of intact parathyroid hormone (260 +/- 227 vs. 213 +/- 153 pg/mL, P < .05) than group 1 patients. No relationship was found between vitamin D storage levels and bone markers, serum calcium, phosphorus, albumin, body mass index, normalized protein catabolic rate, radiologic vascular calcification score, and hip bone mineral density. In multivariate logistic regression analyses, no factors were significantly associated with vitamin D deficiency. Calcidiol deficiency was highly prevalent in a French dialysis population. The associated factors mainly included female sex, diabetes, shorter dialysis duration, and higher intact parathyroid hormone level. Although there are no guidelines for the therapy of patients with chronic kidney disease at stage 5, the usefulness of vitamin D supplementation may be assessed by considering its potential direct action, the need for providing fuel for renal and extrarenal calcitriol production in particular, and the numerous potential favorable effects on health.


Rab7A is required for efficient production of infectious HIV-1.
Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle.


Epidemiology of traumatic brain injury: a population based study in western Sweden.
This study on traumatic brain injury (TBI) is based on prospective and retrospective population based data from a head injury register in Borås. Data was collected from the hospital emergency unit, the discharge register, the regional neurosurgical clinic and the coroner's records during 1 year. This district is mixed urban and rural with a population of 138 000. The 753 cases identified represent an incidence of 546 per 100 000 which includes deaths (0.7%), hospital admissions (67%) and attendance at the emergency department in patients not admitted (32%). Males (644 per 100 000), had 1.46 higher overall rate than females (442 per 100 000). The external causes were dominated by fall from same level (31%) and fall from different level (27%) followed by traffic accidents (16%) and persons hit by objects (15%). The incidence of TBI found in this study is high but well in accordance with earlier published Swedish studies.


Identification of Flavanone 3-Hydroxylase Gene Family in Strawberry and Expression Analysis of Fruit at Different Coloring Stages.
The color of strawberry fruit is an important appearance quality index that affects the marketability of fruit, and the content and type of anthocyanin are two of the main reasons for the formation of fruit color. At present, the research on anthocyanin synthesis mainly focuses on the phenylpropane metabolic pathway, and the F3H gene family is an important member of this metabolic pathway. Therefore, in order to clarify the role of flavanone 3-hydroxylase (F3H) in regulating anthocyanin accumulation in strawberry, we identified F3H gene family members in strawberry and analyzed their bioinformatics and expression at different fruit color stages. The results showed that the strawberry F3H family contains 126 members, which are distributed on seven chromosomes and can be divided into six subgroups. The promoter region of strawberry F3H gene family contains light response elements, abiotic stress response elements and hormone response elements. Intraspecic collinearity analysis showed that there were six pairs of collinearity of the F3H gene. Interspecific collinearity analysis showed that there were more collinearity relationships between strawberry and apple, grape and Arabidopsis, but less collinearity between strawberry and rice. Via tissue-specific expression analysis, we found that the expression levels of FvF3H48, FvF3H120 and FvF3H74 were higher in the stages of germination, growth, flowering and fruit setting. The expression levels of FvF3H42 and FvF3H16 were higher in seeds. The expression levels of FvF3H16 and FvF3H11 were higher in the ovary wall of stage 1, stage 2, stage 3 and stage 5. FvF3H15 and FvF3H48 were highly expressed in the pericardium, anther, receptacle and anther. Real-time fluorescence quantitative PCR showed the expression changes in F3H in the fruit coloring process. The results indicate that the expression levels of most members were higher during the S3 stage, such as FvF3H7, FvF3H16, FvF3H32, FvF3H82, FvF3H89, FvF3H92 and FvF3H112. FvF3H63 and FvF3H104 exhibited particularly high expression levels during the S1 stage, with some genes also showing elevated expression during the S4 stage, including FvF3H13, FvF3H27, FvF3H66 and FvF3H103. FvF3H58, FvF3H69, FvF3H79 and FvF3H80 showed higher expression levels during the S2 stage. These findings lay the groundwork for elucidating the biological functions of the strawberry F3H gene family and the selection of related genes.


A practical guide for evaluating gonadal germ cell tumor predisposition in differences of sex development.
Differences of Sex Development (DSD) includes a wide spectrum of etiologies and phenotypes. A subset of individuals with DSDs are predisposed to gonadal germ cell tumor (GCT). In this setting, GCT risk varies widely, depending on the DSD molecular etiology and penetrance. Prognostication based on molecular diagnosis remains challenging, as natural history data specific to recently identified molecular causes of DSD is lacking. In this review, we provide a framework for the clinical geneticist to consider GCT tumor risk in the patient with DSD. We discuss germ cell development and etiology of GCT growth, along with parameters to consider when recommending prophylactic gonadectomy including fertility, hormonal output, and malignant GTC treatment outcomes. Shortly after the 2006 reorganization of DSD nomenclature, literature reviews of natural history publications stratified GCT risk by a chromosomal, pathological, and hormonal taxonomy. Our 2017 literature review reveals a larger body of publications. However, the broad DSD GCT risk stratification within the 2006 taxonomy remains stable. We discuss precise GCT risk assessment for specific diagnoses, including androgen insensitivity, Smith-Lemli-Opitz, and 46,XY with MAP3K1 mutations and gonadal dysgenesis, as examples. We also examine the GCT risk in non-DSD syndromes, in addition to the cancer risks in DSD patients with dimorphic gonads and genitalia. This review is intended to provide a nuanced assessment of relative germ cell tumor risk in the DSD patient, including modern precise molecular diagnosis, for use by the clinical geneticist.


Waiting times and socioeconomic status: evidence from England.
Waiting times for elective surgery, like hip replacement, are often referred to as an equitable rationing mechanism in publicly-funded healthcare systems because access to care is not based on socioeconomic status. Previous work has established that that this may not be the case and there is evidence of inequality in NHS waiting times favouring patients living in the least deprived neighbourhoods in England. We advance the literature by explaining variations of inequalities in waiting times in England in four different ways. First, we ask whether inequalities are driven by education rather than income. Our analysis shows that education and income deprivation have distinct effects on waiting time. Patients in the first quintile with least deprivation in education wait 9% less than patients in the second quintile and 14% less than patients in the third-to-fifth quintile. Patients in the fourth and fifth most income-deprived quintile wait about 7% longer than patients in the least deprived quintile. Second, we investigate whether inequalities arise "across" hospitals or "within" the hospital. The analysis provides evidence that most inequalities occur within hospitals rather than across hospitals. Moreover, failure to control for hospital fixed effects results in underestimation of the income gradient. Third, we explore whether inequalities arise across the entire waiting time distribution. Inequalities between better educated patients and other patients occur over large part of the waiting time distribution. Moreover we find that the education gradient becomes smaller for very long waiting. Fourth, we investigate whether the gradient may reflect the fact that patients with higher socioeconomic status have a different severity as proxied through a range of types and the number of diagnoses (in addition to age and gender) compared to those with lower socioeconomic status. We find no evidence that differences in severity explain the social gradient in waiting times.


Similarity searching for anticandidal agents employing a repurposing approach.
Fungal infections caused by Candida are still a public health concern. Particularly, the resistance to traditional chemotherapeutic agents is a major issue that requires efforts to develop new therapies. One of the most interesting approaches to finding new active compounds is drug repurposing aided by computational methods. In this work, two databases containing anticandidal agents and drugs were studied employing cheminformatics and compared by similarity methods. The results showed 36 drugs with high similarities to some candicidals. From these drugs, trimetozin, osalmid and metochalcone were evaluated against C. albicans (18804), C. glabrata (90030), and miconazole-resistant strain C. glabrata (32554). Osalmid and metochalcone were the best, with activity in the micromolar range. These findings represent an opportunity to continue with the research on the potential antifungal application of osalmid and metochalcone as well as the design of structurally related derivatives.


Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells.
Persistent hepatitis C virus (HCV) infection leads to chronic hepatitis C (CHC), which often progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The molecular mechanisms that establish CHC and cause its subsequent development into LC and HCC are poorly understood. We have identified a cytoplasmic double-stranded RNA binding protein, Stau1, which is crucial for HCV replication. In this study, Stau1 specifically interacted with the variable-stem-loop region in the 3' NTR and domain IIId of the HCV-IRES in the 5' NTR, and promoted HCV replication and translation. Stau1 coimmunoprecipitates HCV NS5B and a cell factor, protein kinase R (PKR), which is critical for interferon-induced cellular antiviral and antiproliferative responses. Like Stau1, PKR displayed binding specificity to domain IIId of HCV-IRES. Stau1 binds to PKR and strongly inhibits PKR-autophosphorylation. We demonstrated that the transport of HCV RNA on the polysomes is Stau1-dependent, being mainly localized in the monosome fractions when Stau1 is downregulated and exclusively localized in the polysomes when Stau1 is overexpressed. Our findings suggest that HCV may appropriate Stau1 to its advantage to prevent PKR-mediated inhibition of eIF2α, which is required for the synthesis of HCV proteins for translocation of viral RNA genome to the polysomes for efficient translation and replication.


How district health authorities organise cervical screening.
To examine how district health authorities organised cervical screening with respect to Department of Health guidelines and to determine their assessment of the problems encountered. Postal questionnaire sent to all 190 district health authorities in England in 1989. 190 District health authorities in England. Population coverage of screening, quality of smear testing, and follow up of abdominal test results in comparison with national guidelines for district cervical screening services, and problems encountered by districts. Replies were received from 178 (94%) of districts, in 143 of which the person named as responsible for cervical screening contributed. All districts implemented a computer managed scheme, 150 by the target date of 31 March 1988, but not all of these conformed with the guidelines. At the time of the survey only just over half called women in the target age group of 20-64 and only 70% expected to meet the target date of 13 March 1993 for completing the call. Considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage, quality of testing, and follow up of abnormal results. The problems most commonly identified by the districts (n = 174) were laboratory workload (107, 61%), computer software (104, 60%), availability of resources (78, 45%), non-attendance (77, 44%), rate of opportunistic screening (62, 36%), and investigation and treatment (60, 34%). Current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer.


Segmental early relaxation phenomenon: incidence, clinical characteristics, and significance in stress echocardiography.
To evaluate the incidence, patient characteristics, and clinical significance of segmental early relaxation phenomenon (SERP) in stress echocardiography. Retrospective interpretation of digitized rest/stress echocardiographic images of 244 consecutive patients undergoing exercise or dobutamine echocardiography with subsequent patient follow-up for outcomes. Tertiary care referral center. Two hundred forty-four consecutive patients referred for stress echocardiography (exercise or dobutamine) for various clinical indications. None. SERP was diagnosed as a sudden outward motion of a portion of the left ventricle during early diastole (using frame-by-frame analysis) after peak systole prior to mitral valve opening at rest and after stress. Stress-associated SERP was observed in 71 patients (29.1%), with 25 patients having SERP in more than one segment. Five patients had resting SERP, with two persisting during stress. Ninety-six of 3,658 analyzed segments were positive for SERP. The apical septum and midseptum were most commonly involved in 49% and 18%, respectively. Only 5 of 96 patients (5.2%) had new hypokinesis and SERP in the same segment. No significant differences existed in demographic, clinical, or echocardiographic variables in patients with and without SERP. Follow-up revealed no significant differences in event rates in those with and without SERP. This is the first stress echocardiographic study demonstrating that SERP is a distinct and relatively common stress echocardiographic phenomenon occurring in early diastole regardless of type of stress. SERP occurs predominantly in apical and midseptum in the distribution of the left anterior descending coronary artery. It should not be mistaken for atypical septal motion, ischemia, or dyskinesia, and does not seem related solely to the presence of underlying coronary disease or stress-induced ischemia. No adverse long-term outcomes are seen in patients with SERP and no inducible ischemia.


Cloning, expression and biochemical characterization of the cholesterol oxidase CgChoA from Chryseobacterium gleum.
Cholesterol oxidases are important enzymes for applications such as the analysis of cholesterol in clinical samples, the synthesis of steroid derived drugs, and are considered as potential antibacterial drug targets. The gene choA encoding a cholesterol oxidase from Chryseobacterium gleum DSM 16776 was cloned into the pQE-30 expression vector and heterologously expressed in Escherichia coli JM109 co-transformed with pRARE2. The N-terminally His-tagged cholesterol oxidase (CgChoA) was assigned to be a monomer in solution by size exclusion chromatography, showed a temperature optimum of 35°C, and a pH optimum at 6.75 using 0.011 M MOPS buffer under the tested conditions. The purified protein showed a maximum activity of 15.5 U/mg. CgChoA showed a Michaelis-Menten like kinetic behavior only when the substrate was dissolved in water and taurocholate (apparent K(m) = 0.5 mM). In addition, the conversion of cholesterol by CgChoA was studied via biocatalytic batches at analytical scale, and cholest-4-en-3-one was confirmed as product by HPLC-MS. CgChoA is a true cholesterol oxidase which activity ranges among the high performing described cholesterol oxidases from other organisms. Thus, the enzyme broadens the available toolbox of cholesterol oxidases for e.g. synthetic and biosensing applications.


Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast-like synoviocytes of collagen induced arthritic rats.
To investigate the effects of Paeoniflorin (Pae) on inflammatory mediators and G protein-coupled signaling in fibroblast-like synoviocytes (FLS) from collagen induced arthritic (CIA) rats. SD rats were injected with type II collagen. Pae (25, 50, 100 mg. kg(-1)) was administered to CIA rats. The inflammation of CIA rats was evaluated by paw swelling, arthritis index and histopathology of joints. FLS were isolated and cultured. Interleukin (IL)-1 activity was measured by the 3H-TdR-intake method Tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and cAMP were measured by radioimmunoassay. Protein kinase A (PKA) was assessed by luminescent kinase assay. Gi was detected by Western blot. Inflammation in CIA rats was accompanied by hyperplastic synovium, pannus and cartilage erosion in joints. IL-1 activity and Gi expression increased, PGE2 and TNF-alpha production were enhanced, but cAMP level and PKA activity decreased. Pae significantly suppressed the inflammatory response and inflammatory mediators (IL-1, TNF-alpha and PGE2) in vivo. Pae inhibited Gi expression and restored cAMP level and PKA activity in FLS of CIA rats in vivo and vitro. Inflammatory mediators and G protein-coupled signaling were associated with the pathogenesis of synovitis in CIA rats. Pae, as a new monomer, had anti-inflammatory effects on the animal model of CIA in rats, but also had regulatory effects on FLS from CIA rats in vitro. These results highlight Pae as a good candidate for therapeutic intervention in RA.


Gastrointestinal volatile fatty acid concentrations and pH in cats.
To measure volatile fatty acid (VFA) concentrations and pH in the gastrointestinal tracts of healthy adult cats fed a commercial dry cat food. 14 cats. The gastrointestinal tracts were excised immediately after euthanasia and divided into 6 sections (stomach, duodenum, jejunum, ileum, proximal portion of the colon, and distal portion of the colon). Luminal contents were collected from each segment, pH was measured, and contents were centrifuged. The supernatant was analyzed for acetate, proprionate, butyrate, isobutyrate, valerate, and isovalerate concentrations by use of gas chromatography. Mean total VFA concentrations were lowest in the stomach (20 mmol/L); increased through the duodenum, jejunum, and ileum (30, 29, and 41 mmol/L, respectively); and were greatest in the proximal and distal portions of the colon (109 and 131 mmol/L, respectively). Estimated mean total VFA amounts were low (<600 micromol) throughout all segments of the gastrointestinal tract; pH values increased from the stomach through the ileum and subsequently decreased in the colon. Total VFA concentrations in the colon were comparable to values reported for the forestomach of ruminants and large intestines of monogastric animals, whereas values in the small intestine were higher than reported for other species. Total VFA amounts were low, consistent with the short, nonvoluminous gastrointestinal tract of carnivores. Luminal pH varied throughout the gastrointestinal tract in a pattern similar to other monogastric animals. Volatile fatty acids probably contribute minimal metabolic energy in cats but may be important in the maintenance of local mucosal health.


Impact of prenatal diagnosis on the morbidity associated with ureterocele management.
We postulated that prenatal detection of ureteroceles has a positive impact on the natural history and clinical outcome of ureteroceles in duplex system. Between 1992 and 2000, 95 children underwent surgery for a ureterocele in a duplex system. We evaluated the impact of prenatal diagnosis in 40 cases versus postnatal diagnosis in 55 on morbidity, as measured by postoperative urinary tract infection and secondary procedures, while controlling for ureterocele type and the initial surgical approach. Mean followup in the 2 groups was 3.9 years. Preoperatively the reflux rate was 51% in the prenatal and 66% in the postnatal groups. Preoperatively urinary tract infections were less common in the prenatal group (12% versus 84%). Mean age at initial intervention in prenatally and postnatally diagnosed patients was 6 and 31 months, respectively. Postoperatively the urinary tract infection rate was double in postnatally diagnosed patients. Overall postoperatively reflux was similar in the 2 groups and grades III to V reflux with urinary tract infection accounted for 14 of the 21 secondary bladder procedures (67%). After initial endoscopic decompression none of the prenatally diagnosed patients with intravesical ureteroceles required reoperation, whereas 6 (50%) with extravesical ureteroceles required reoperation. All 10 prenatally diagnosed extravesical ureteroceles treated with partial nephrectomy were cured. Overall the secondary procedure rate in the postnatal group was higher than in the prenatal group (46% versus 20%, p = 0.02). Also, there was a difference in the reoperation rate in the endoscopic decompression group according to mode of presentation (p = 0.03) and a difference when comparing endoscopic treatment with partial nephrectomy in all patients (p = 0.02). Prenatal diagnosis decreases morbidity and potential adverse outcomes related to infection. Overall prenatal diagnosis is associated with a decreased rate of secondary procedures independent of the type of ureterocele. Prenatally diagnosed intravesical ureteroceles may be cured by endoscopic incision alone but for extravesical ureteroceles partial nephrectomy appears to be more definitive.


[Oropharyngeal anthrax].
We report on a 46-year old man suffering from the oropharyngeal form of human anthrax. The patient presented with a sore throat and extensive swelling of the right neck, the oropharynx and especially the right tonsil. The skin of the mandibular and submandibular region showed vesicular lesions followed by ulcerations resulting in a blackish eschar. The diagnosis was verified by bacteriological culture. Thus, in cases of known exposure, in areas where anthrax is endemic or in immigrant workers coming from such areas, infection with bacillus anthracis should be included in the differential diagnosis of inflammatory oedematous lesions of the oropharynx.


Surgical Treatment of Dentofacial Deformities Caused by Juvenile Idiopathic Arthritis.
The purpose of our retrospective study was to evaluate the results of orthognathic treatment, distraction osteogenesis, and/or prosthetic reconstruction of the temporomandibular joints in patients with juvenile idiopathic arthritis (JIA).Twelve patients with severely affected temporomandibular joints (TMJs) and reduced ramus height were treated with mandibular advancement with orthognathic surgery (11) and additional bilateral or unilateral mandibular ramus distraction (3) or additional bilateral or unilateral prosthetic reconstruction of the TMJ (3). One patient was treated surgically with bilateral TMJ prosthetic reconstruction only. The patients were followed up clinically and radiologically with emphasis on healing, TMJ function, stability of the occlusion, skeletal stability, and facial appearance for an average of 2.3 years after the final surgery. The mean mandibular advancement was 10.1 mm. The mean relapse at pogonion was 2.1 mm, which represents 20.8% of the surgical advancement. The occlusion was stable in 11/12 patients. The TMJ function was good and the facial esthetics improved in all patients. Orthognathic treatment and mandibular ramus distraction osteogenesis provide beneficial lengthening of the mandibular body in JIA patients with asymptomatic and stabile condyles. In adult patients with relapse of the disease or postoperative condylar relapse prosthetic total joint replacement is a reliable and safe alternative.


Quality of life after switching from well-controlled vitamin K antagonist to direct oral anticoagulant: Little to GAInN.
Direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) prevent thromboembolism in atrial fibrillation (AF). DOAC have a fixed dosing regimen and obviate INR monitoring. Therefore, DOAC presumably affect quality of life (QoL) less than VKA. However, some VKA users appreciate the monitoring. A high time in the therapeutic range (TTR) leads to a lower impact on QoL. We assessed the influence of switching from well-controlled VKA to a DOAC on QoL. In the GAInN study, 241 patients with AF, a TTR ≥ 70%, and neither bleeding nor thrombosis while on VKA were randomised to switching to DOAC (n = 121) or continuing VKA (n = 120). Health-related (SF-36) and anticoagulation-related QoL (PACT-Q) was assessed at baseline and after six and twelve months of follow-up. SF-36 development did not differ between groups. After one year, average PACT-Q Convenience improvement was 2.5 (0.3-4.7) higher on DOAC. DOAC users were 6percentage points (95%CI -4-16) more likely to improve >5 points on Convenience; 22 pp. (95%CI 1-43) in patients who scored <95/100 at baseline. The probability to meaningfully improve on PACT-Q Satisfaction was 12 pp. (95%CI 0-25) higher on DOAC. However, 5 (4.1%) and 4 (3.3%) DOAC users resumed VKA because of side-effects and patient preference. Switching from well-controlled VKA to DOAC for AF leads to a higher probability of improved PACT-Q convenience and satisfaction, but also to a higher risk of side-effects. Arguably only patients who are not satisfied with VKA should switch, because they have more to gain by switching.


Functional annotation of the T-cell immunoglobulin mucin family in birds.
T-cell immunoglobulin and mucin (TIM) family molecules are cell membrane proteins, preferentially expressed on various immune cells and implicated in recognition and clearance of apoptotic cells. Little is known of their function outside human and mouse, and nothing outside mammals. We identified only two TIM genes (chTIM) in the chicken genome, putative orthologues of mammalian TIM1 and TIM4, and cloned the respective cDNAs. Like mammalian TIM1, chTIM1 expression was restricted to lymphoid tissues and immune cells. The gene chTIM4 encodes at least five splice variants with distinct expression profiles that also varied between strains of chicken. Expression of chTIM4 was detected in myeloid antigen-presenting cells, and in γδ T cells, whereas mammalian TIM4 is not expressed in T cells. Like the mammalian proteins, chTIM1 and chTIM4 fusion proteins bind to phosphatidylserine, and are thereby implicated in recognition of apoptotic cells. The chTIM4-immunoglobulin fusion protein also had co-stimulatory activity on chicken T cells, suggesting a function in antigen presentation.


Role of fibroblast growth factor 23 and klotho cross talk in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia that mainly affects the elderly. Several reports have demonstrated that aging is involved in the underlying pathogenic mechanisms of IPF. α-Klotho (KL) has been well characterized as an "age-suppressing" hormone and can provide protection against cellular senescence and oxidative stress. In this study, KL levels were assessed in human plasma and primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF-FB) and in lung tissue from mice exposed to bleomycin, which showed significant downregulation when compared with controls. Conversely, transgenic mice overexpressing KL were protected against bleomycin-induced lung fibrosis. Treatment of human lung fibroblasts with recombinant KL alone was not sufficient to inhibit transforming growth factor-β (TGF-β)-induced collagen deposition and inflammatory marker expression. Interestingly, fibroblast growth factor 23 (FGF23), a proinflammatory circulating protein for which KL is a coreceptor, was upregulated in IPF and bleomycin lungs. To our surprise, FGF23 and KL coadministration led to a significant reduction in fibrosis and inflammation in IPF-FB; FGF23 administration alone or in combination with KL stimulated KL upregulation. We conclude that in IPF downregulation of KL may contribute to fibrosis and inflammation and FGF23 may act as a compensatory antifibrotic and anti-inflammatory mediator via inhibition of TGF-β signaling. Upon restoration of KL levels, the combination of FGF23 and KL leads to resolution of inflammation and fibrosis. Altogether, these data provide novel insight into the FGF23/KL axis and its antifibrotic/anti-inflammatory properties, which opens new avenues for potential therapies in aging-related diseases like IPF.


Uremic pruritus.
Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient's quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) μ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as μ-opioid-receptor-antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on 'high urgency'-status, as successful kidney transplantation will relieve patients from CKD-aP.


Improved Reversed Phase Chromatography of Hydrophilic Peptides from Spatial and Temporal Changes in Column Temperature.
Reversed phase chromatography is an established method for peptide separation and frequently coupled to electrospray ionization-mass spectrometry for proteomic analysis. Column temperature is one parameter that influences peptide retention and elution, but it is often overlooked as its implementation requires additional equipment and method optimization. An apparatus that allows temperature manipulation in three areas of a two-column setup was evaluated for improvements in chromatography. Using commercially available standards, we demonstrate that a low column temperature (0 °C) during sample loading enhances the peak shape of several bovine serum albumin hydrophilic peptides. For digested HeLa lysates, approximately 15% more peptide identifications were obtained by increasing the precolumn temperature to 50 °C after the 500 ng sample was loaded at a low temperature. This method also identified additional early eluting peptides with grand average of hydropathicity values less than -2. We also investigated the effect of cooler column temperatures on peptides with post-translational modifications. It was possible to minimize the coelution of an isoaspartylated peptide and its unmodified version when the analytical column temperature was decreased to 5 °C. Aside from demonstrating the utility of lower temperatures for improved chromatography, its application at specific locations and time points is critical for peptide detection and separation.


Direct observation of spatially heterogeneous single-layer graphene oxide reduction kinetics.
Graphene oxide (GO) is an important precursor in the production of chemically derived graphene. During reduction, GO's electrical conductivity and band gap change gradually. Doping and chemical functionalization are also possible, illustrating GO's immense potential in creating functional devices through control of its local hybridization. Here we show that laser-induced photolysis controllably reduces individual single-layer GO sheets. The reaction can be followed in real time through sizable decreases in GO's photoluminescence efficiency along with spectral blueshifts. As-produced reduced graphene oxide (rGO) sheets undergo additional photolysis, characterized by dramatic emission enhancements and spectral redshifts. Both GO's reduction and subsequent conversion to photobrightened rGO are captured through movies of their photoluminescence kinetics. Rate maps illustrate sizable spatial and temporal heterogeneities in sp(2) domain growth and reveal how reduction "flows" across GO and rGO sheets. The observed heterogeneous reduction kinetics provides mechanistic insight into GO's conversion to chemically derived graphene and highlights opportunities for overcoming its dynamic, chemical disorder.


pp60c-src associates with the SH2-containing inositol-5-phosphatase SHIP1 and is involved in its tyrosine phosphorylation downstream of alphaIIbbeta3 integrin in human platelets.
SH2-containing inositol-5-phosphatase 1 (SHIP1) was originally identified as a 145 kDa protein that became tyrosine-phosphorylated in response to multiple cytokines. It is now well established that SHIP1 is specifically expressed in haemopoietic cells and is important as a negative regulator of signalling. We found recently that SHIP1 was present in human blood platelets as an Ins(1,3,4, 5)P(4)-phosphatase and a PtdIns(3,4,5)P(3)-5-phosphatase that became tyrosine-phosphorylated and was relocated to the cytoskeleton in an integrin-dependent manner. Here we report biochemical and pharmacological evidence that the tyrosine kinase pp60(c-src) is constitutively associated with SHIP1 and is involved in its tyrosine phosphorylation downstream of integrin engagement in thrombin-activated human platelets. The use of cytochalasin D allowed us to demonstrate that the actin cytoskeleton reorganization induced on thrombin stimulation was not required for its integrin-mediated phosphorylation. Moreover, the integrin-dependent relocation of SHIP1 to the cytoskeleton did not require its tyrosine phosphorylation. These results suggest that SHIP1 is first recruited to the integrin-linked signalling complexes and then becomes tyrosine-phosphorylated through a Src-kinase-dependent mechanism but independently of the actin cytoskeleton reorganization.


A coordination polymer based on dinuclear (pyrazinyl tetrazolate) copper(ii) cations and Wells-Dawson anions for high-performance supercapacitor electrodes.
A new coordination polymer, (H2bpe)(Hbpe)2{[Cu(pzta)(H2O)][P2W18O62]}·5H2O (1) (pztaH = 5-(2-pyrazinyl) tetrazolate, bpe = bis(4-pyridyl)ethylene), was synthesized by the hydrothermal method. The structure was determined by single crystal X-ray diffraction analyses and further characterized by the SEM, EDS, BVS, FTIR, and PXRD techniques. In 1, the [P2W18O62]6- (P2W18) clusters as bidentate connectors link [Cu(pzta)(H2O)]24+ dinuclear copper(ii) complexes to form inorganic-organic chains. These chains and the [H2bpe]2+ counter-cations are fused together via hydrogen bonding to form a 3D supramolecular architecture. While 1 was employed as the electrode in a supercapacitor, the cycling stability (90.7% capacitance retention after 1000 circles) and specific capacitance (168 F g-1 at a current density of 5 A g-1) of the 1-based electrode are better than those of the parent α-K6P2W18O62-based electrode, demonstrating more outstanding electrochemical performances of 1. Besides, the 1-based electrode showed excellent electrocatalytic activities towards the reduction of H2O2 and KIO3.


Anatomy of the auditory cortex then and now.
Using neuroanatomical investigations in the macaque, Deepak Pandya and his colleagues have established the framework for auditory cortex organization, with subdivisions into core and belt areas. This has aided subsequent neurophysiological and imaging studies in monkeys and humans, and a nomenclature building on Pandya's work has also been adopted by the Human Connectome Project. The foundational work by Pandya and his colleagues is highlighted here in the context of subsequent and ongoing studies on the functional anatomy and physiology of auditory cortex in primates, including humans, and their relevance for understanding cognitive aspects of speech and language.


Novel smooth muscle cell lines from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene. Temperature-dependent expression of smooth muscle myosin heavy chain-1 and calponin genes.
We have established novel vascular smooth muscle cell lines (SVS30 and SVS24 cells) which retain the expression of specific markers for smooth muscle cells, such as alpha-actin, smooth muscle myosin heavy chain-1, and calponin, from transgenic mice harboring the temperature-sensitive SV40 large T-antigen gene. SVS cell lines showed temperature-dependent growth and the expression of SV40 large T-antigen. Interestingly, protein and mRNA levels of smooth muscle myosin heavy chain-1 and calponin seen in culture at the non-permissive temperature (39 degrees C) were higher than those at the permissive temperature (33 degrees C). These results suggest that SV40 large T-antigen affects the expression of smooth muscle-specific markers in SVS cell lines, and that some of the characters in SVS cell lines can be controlled by culture temperature. SVS cell lines should be quite valuable tools with which to study the regulation of phenotypic modulation of smooth muscle cells, and to identify smooth muscle specific transcription factors which involve the expression of smooth muscle myosin heavy chain-1 and calponin genes.


Surface versus intramuscular electrodes for electromyography of superficial and deep muscles.
The relative selectivity of surface electrodes placed over the gastrocnemius and soleus muscles in the standard manner was determined by comparing the electromyogram from these electrodes to the electromyogram from wire electrodes inserted into the soleus, gastrocnemius, and tibialis posterior muscles. Muscle activity was elicited in 11 normal subjects by performing six manual muscle tests. Three of the tests followed the standard technique and three were modifications designed to provide better differentiation of muscle action. All electromyographic data were quantified by computer integration and normalized to cancel out sampling inconsistency. None of the muscle tests totally restricted activity to the designated muscle, but the tests did determine which was the strongest participant. During the standard specific gastrocnemius and soleus muscle tests, the corresponding surface electrode provided a lower electromyogram than did the matching wire electrode; that is, the surface-to-wire-electrode ratio was less than one (gastrocnemius = 0.74, soleus = 0.58). This ratio was greater than one when the electromyogram was being recorded from one muscle while testing another muscle (gastrocnemius = 1.55, soleus = 1.92). The mathematical model relating surface-electrode values to the wire-electrode data from all three muscles identified 60 percent of the surface gastrocnemius electrode electromyogram as arising from that muscle, while only 36 percent of the soleus surface electrode data related to the activity of the soleus: Sg = .19Ws + 60Wg + .13Wt + .08Wo and Ss = .36Ws + .31Wg + .22Wt + .11Wo.


Free energy of ligand binding to protein: evaluation of the contribution of water molecules by computational methods.
One of the more challenging issues in medicinal chemistry is the computation of the free energy of ligand binding to macromolecular targets. This allows for the screening of libraries of chemicals for fast and inexpensive identification of lead compounds. Many attempts have been made and several algorithms have been developed for this purpose. Whereas enthalpic contributions are evaluated using methods and equations for which there is a reasonable consensus among researchers, the entropic contribution is evaluated using very different, and, in some cases, very approximate methods, or it is entirely ignored. Entropic contributions are of primary importance in the formation of many ligand-protein complexes, as well as in protein folding. The hydrophobic interaction, associated with the release of water molecules from the protein active site and the ligand, plays a significant role in complex formation, predominantly contributing to the total entropy change and, in some cases, to the total free energy of binding. There are distinct approaches for the evaluation of the contribution of water molecules to the free energy of binding based on Newtonian mechanics force fields, multi-parameter empirical scoring functions and experimental force fields. This review describes these methods -- discussing both their advantages and limitations. Particular emphasis will be placed on HINT (Hydropatic INTeractions), a "natural" force field that takes into account in a unified way enthalpic and entropic contributions of all interacting atoms in protein-ligand complexes, including released and structured water molecules. As a case-study, the contribution of water molecules to the binding free energy of HIV-1 protease inhibitors is evaluated.


Marrow cell transplantation for infantile hypophosphatasia.
An 8-month-old girl who seemed certain to die from the infantile form of hypophosphatasia, an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), underwent the first trial of bone marrow cell transplantation for this heritable type of rickets. After cytoreduction, she was given T-cell-depleted, haplo-identical marrow from her healthy sister. Chimerism in peripheral blood and bone marrow became 100% donor. Three months later, she was clinically improved, with considerable healing of rickets and generalized skeletal remineralization. However, 6 months post-transplantation, worsening skeletal disease recurred, with partial return of host hematopoiesis. At the age of 21 months, without additional chemotherapy or immunosuppressive treatment, she received a boost of donor marrow cells expanded ex vivo to enrich for stromal cells. Significant, prolonged clinical and radiographic improvement followed soon after. Nevertheless, biochemical features of hypophosphatasia have remained unchanged to date. Skeletal biopsy specimens were not performed. Now, at 6 years of age, she is intelligent and ambulatory but remains small. Among several hypotheses for our patient's survival and progress, the most plausible seems to be the transient and long-term engraftment of sufficient numbers of donor marrow mesenchymal cells, forming functional osteoblasts and perhaps chondrocytes, to ameliorate her skeletal disease.


Large FK506-binding proteins shape the pharmacology of rapamycin.
The immunosuppressant and anticancer drug rapamycin works by inducing inhibitory protein complexes with the kinase mTOR, an important regulator of growth and proliferation. The obligatory accessory partner of rapamycin is believed to be FK506-binding protein 12 (FKBP12). Here we show that rapamycin complexes of larger FKBP family members can tightly bind to mTOR and potently inhibit its kinase activity. Cocrystal structures with FKBP51 and FKBP52 reveal the modified molecular binding mode of these alternative ternary complexes in detail. In cellular model systems, FKBP12 can be functionally replaced by larger FKBPs. When the rapamycin dosage is limiting, mTOR inhibition of S6K phosphorylation can be enhanced by FKBP51 overexpression in mammalian cells, whereas FKBP12 is dispensable. FKBP51 could also enable the rapamycin-induced hyperphosphorylation of Akt, which depended on higher FKBP levels than rapamycin-induced inhibition of S6K phosphorylation. These insights provide a mechanistic rationale for preferential mTOR inhibition in specific cell or tissue types by engaging specific FKBP homologs.


[Bruton tyrosine kinase inhibitors. What does the oncohematologist and the cardiologist need to know?]
Advances in knowledge incorporated in the last decade have modified the treatment paradigm in most of the malignant hematological diseases. In particular, the introduction of Bruton tyrosine kinase inhibitors (BTKi) and other target drugs together with new monoclonal antibodies have become agents of choice for both chronic lymphocytic leukemia (CLL) and other peripheral "B" lymphomas such as mantle cell lymphoma (MCL). The results of efficacy against genotoxic therapy are so successful that the end of chemoimmunotherapy, especially for CLL, is already a postulate recognized by the main research groups. On the other hand, the new drugs modified the profile of adverse events, which forced the development of new subspecialties such as cardio-oncology, which currently constitutes a bastion for the rational management of these patients. This review aims to highlight the current state of knowledge on these pathologies, pharmacological principles together with new adverse events of iBTK and the invaluable contribution of cardiology for correct management of these patients.


The population biology of bacterial plasmids: a priori conditions for the existence of mobilizable nonconjugative factors.
A mathematical model for the population dynamics of nonconjugative plasmids that can be mobilized by conjugative factors is presented. In the analysis of the properties of this model, primary consideration is given to the conditions under which these nonself-transmissible extrachromosomal elements could become established and would be maintained in bacterial populations. The results of this analysis demonstrate the existence of conditions where, as a consequence of infectious transmission via mobilization, nonconjugative plasmids could become established and be maintained even when the bacteria carrying them have lower reproductive fitnesses than plasmid-free members of the population. However, these existence conditions are stringent and suggest therefore, that it is highly unlikely that plasmids of this type would become established and maintained without some direct selection favoring their carriage. The general implications of these results and limitations of the model are discussed. Brief consideration is also given to the implications of these theoretical findings to the problems of the spread of multiple antibiotic resistance plasmids (R-factors) and the risk of contaminating natural populations of bacteria with chimeric plasmids produced by work with recombinant DNA.


Profiling tumor-associated autoantibodies for the detection of colon cancer.
The purpose of the present study was to screen the autoantibody signature of colon cancers to develop serum markers for colon cancer detection. A phage cDNA expression library of colon cancer was built. The library was sequentially screened by a pool of 10 colon cancer sera, goat antihuman IgG, and a pool of two healthy sera to identify phage-expressed antigens recognized by tumor-associated antibodies. The clones picked out by these screening were subjected to a training set with 24 colon cancer sera and 24 healthy sera. The antigen combination, which got the most satisfactory classification, was tested by an independent set of 24 colon cancer sera with equal number of sera from normal donors. The carcinoembryonic antigen (CEA) level of these sera was detected for the additional classification analysis with or without the antigen combination. A cDNA expression library consisting of 2 x 10(6) primary clones was prepared. After three turns of screening, 24 antigens recognized by tumor-associated antibodies were picked out for serum marker identification. The training set showed that a six-marker combination got the most satisfactory classification in a logistic regression model; leave-one-out validation achieved 91.7% sensitivity and 91.7% specificity. In a testing set with this marker panel, we correctly predicted 85% of the samples. Although according to CEA level alone, we correctly predicted 75% of the samples with 42% of cancer patients misclassified. When CEA was combined with the six markers, the sensitivity and specificity increased to 91.7% and 95.8%, respectively. The six antigen sequences in the phage display system are relatively short peptides. Only two of them showed homology to known protein sequences. Autoantibodies against phage-expressed antigens derived from colon cancer tissues could be used as serum markers for the detection of colon cancer.


Dysbiosis is not present in horses with fecal water syndrome when compared to controls in spring and autumn.
Fecal water syndrome (FWS) is long-standing and common in horses, particularly in central Europe. No large epidemiological data sets exist, and the cause remains elusive. Dysbiosis could play a role in pathogenesis. To evaluate whether dysbiosis is present in horses with FWS when compared to stable-matched control horses in spring and autumn. Fecal samples were collected from horses with FWS (n = 16; 9 mares, 7 geldings) and controls (n = 15; 8 mares, 7 geldings). The bacterial microbiome of samples collected in spring and autumn of 2016 was analyzed using high-throughput sequencing. Differences in relative abundance of bacterial taxa, alpha diversity, and beta diversity indices were assessed between horses with FWS and controls based on season. Differences in microbial community composition based on time point and health status were not observed on any taxonomic level. Limited differences were seen on linear discriminant analysis effect size analysis. No difference in alpha diversity indices was observed including richness, diversity based on health status, or time point. No effect of health status on microbial community membership structure was observed. Limited differences were found in the bacterial microbiota of horses with and without FWS, regardless of season. Further research is needed to elucidate the role of microbiota in the development of FWS.


Pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure and diagnostic value of sTREM-1, sCD163, and sTWEAK.
To investigate the pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure as well as the diagnostic value of soluble myeloid cell expression triggering receptor-1 (sTREM-1), soluble CD163 (sCD163) and soluble tumor necrosis factor-like weak inducing factor (sTWEAK). A total of 72 patients with pulmonary infection who were hospitalized with chronic heart failure from December 2017 to December 2019 in the Department of Cardiology of Hebei Baoding Huaying Hospital of Traditional Chinese Medicine, China, were selected as the infection group, seventy-two patients without pulmonary infection who were hospitalized with chronic heart failure were selected as the non-infection group, and 50 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group. The distribution characteristics of pathogens in the infection group were statistically analyzed. The levels of sTREM-1, S CD163 and STweak in serum of patients with different infection severity and different cardiac function grades were compared among the three groups. Receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of the three indicators for the adverse prognosis of patients in hospital. A total of 76 strains of pathogens were cultured from two hospitalized patients with pulmonary infection of chronic heart failure, among which 43 strains (56.58%) were gram-negative bacteria, 29 strains (38.15%) were gram-positive bacteria, and four strains (5.26%) were fungi. The levels of sTREM-1 and sCD163 in the control group, non-infection group and infection group were gradually increased (p<0.05), while there was no difference in sTWEAK between the infection group and the non-infection group (p>0.05). In the infection group, the expression levels of sTREM-1 and sCD163 increased with the severity of infection, with statistically significant differences (p<0.05), while there was no statistically significant difference in the expression level of sTWEAK among different infection severity (p>0.05). The higher the cardiac function grade of patients in the infection group, the higher the levels of sTREM-1 and sCD163, and the lower the level of sTWEAK, with a statistical significance (p<0.05). ROC analysis results showed that the serum sTREM-1, sCD163, and sTWEAK levels for the poor prognosis of patients with CHF combined with lung infection had areas under the curve of 0.864, 0.870, and 0.822, respectively, and the 95% CI values were 0.787-0.941, 0.795-0.945 and 0.733-0.910, respectively, all p<0.001. Pulmonary infection in hospitalized patients with chronic heart failure is mainly caused by gram-negative bacteria. Detection of sTREM-1, sCD163, and sTWEAK levels is of certain value in judging the condition and prognosis, which is worthy of clinical promotion.


Acylsilane directed aromatic C-H alkenylations by ruthenium catalysis.
A ruthenium-catalyzed C-H alkenylation of aroylsilanes with electron-deficient alkenes was developed, using acylsilane as the directing group. The mild reaction conditions enable the tolerance of a wide scope of functionalities such as OMe, F, Cl, Br and CF3, providing a convenient and highly effective method for the synthesis of styrene derivatives bearing acylsilane. Steroid and heterocycles such as furan and thiophene were also well tolerated. Furthermore, acylsilane was efficiently converted to the corresponding aldehyde or carboxylic acid.


The technique of therapeutic apheresis. Removal of abnormal blood elements may succeed when all else fails.
Therapeutic apheresis is a generic term that refers to removal of abnormal blood cells and plasma constituents. The terms "plasmapheresis," "leukapheresis," and "erythrocytapheresis" describe the specific blood element that is removed. Apheresis therapies can be performed in the ICU to manage a number of neurologic, hematologic, and autoimmune disorders, including myasthenia gravis, Guillain-Barré syndrome, sickle-cell disease, and Goodpasture's syndrome. Apheresis procedures generally require two points of contact with the circulation--one for blood withdrawal and one for return; the withdrawal site should sustain a flow rate of at least 50 mL/min. Although apheresis is generally quite safe, hemodynamic instability, hypocalcemia, and dilutional coagulopathy can occur.


Improving outcomes in high-risk, nonmetastatic renal cancer: new data and ongoing trials.
High-risk, localized renal cancer is associated with recurrence rates of up to 75% at 10 years. The outcomes of patients at this disease stage depend on optimal patient stratification, surgical management and systemic therapy selection. Current evidence does not support the use of adjuvant therapy in patients with high-risk, localized disease. During the past 12 months, the results of large, randomized-controlled trials of adjuvant tyrosine kinase inhibitor (TKI) treatment, such as ASSURE and S-TRAC, have been published, but their findings are conflicting. Whether TKIs will become standard of care in the adjuvant setting depends on the long-term data from ongoing trials. In addition, several new trials that evaluate the utility of novel immune checkpoint inhibitors in this patient group are currently recruiting. The management of renal cancer is likely to evolve at a rapid pace over the next few years and matching patients with the appropriate therapeutic regimen is likely to be a focus of future research.


Improving early recognition of delirium using SQiD (Single Question to identify Delirium): a hospital based quality improvement project.
Delirium is a serious condition associated with poor outcomes which can be prevented and treated if recognised early. Older people and people with dementia or severe illness are more at risk of delirium. SQiD is a simple prompt question which asks, "Is this patient more confused than before?" Focusing specifically on patients aged 75 and over, this project aimed to increase awareness and usage of SQiD to help improve early recognition of delirium, in accordance with the Healthcare Improvement Scotland national initiative. This project was carried out by two student nurses during an eight week clinical placement in the acute surgical receiving unit (ASRU) of Ninewells Hospital, Dundee, Scotland. Qualitative and quantitative methodology was used to establish baseline data which revealed that only 35% of the multidisciplinary team (MDT) were aware of SQiD, with only 15% using SQiD. Initial activities involved raising awareness of SQiD by means of information cards and posters. Once awareness was raised, the usage of the SQiD question by nurses was tested. Finally, the SQiD question was incorporated into the nursing care round forms and usage recorded. Following these awareness raising activities we noted an increase of 83% awareness and 20% use of SQiD. Incorporating the SQiD question into the hourly care round forms increased awareness to 100% and usage to 50%. Although this small scale project could be viewed as a success, the requirements for sustainability depend upon further implementation and spreading of the change. Sustained improvement is also dependent upon the implementation of the care rounds. As nursing students, undertaking this improvement project has provided valuable lessons in both quality improvement science and personal learning. The improved knowledge and understanding of effective communication and the intricacies of team working is transferrable and can be applied to future nursing practice.


Toxic effects of chromium (VI) by maternal ingestion on liver function of female rats and their suckling pups.
Potassium dichromate (K(2)Cr(2)O(7)) is an environmental contaminant widely recognized as a carcinogen, mutagen, and teratogen toward humans and animals. This study investigated the effects of K(2)Cr(2)O(7) on the hepatic function of pregnant and lactating rats and their suckling pups. Experiments were carried out on female Wistar rats given 700 ppm of K(2)Cr(2)O(7) in their drinking water from the 14th day of pregnancy until day 14 after delivery. Hepatotoxicity was objectified by the significant increase in liver malondialdehyde content and a significant accumulation of chromium in this soft tissue. Moreover, exposure to K(2)Cr(2)O(7) induced a decrease of glutathione, nonprotein thiols, and vitamin C in the liver of mothers and their suckling pups. Alteration of the antioxidant system in the treated group was confirmed by the significant decline of antioxidant enzyme activities such as catalase, glutathione peroxidase, while liver superoxide dismutase activity increased in mothers and decreased in their offspring. It was found that K(2)Cr(2)O(7) induced liver damages as evidenced by the elevation of plasma aminotransferases, lactate dehydrogenase activities, and bilirubin levels. Impairment of the hepatic function corresponded histologically. Our investigation revealed hemorrhage, leukocytes infiltration cells, and necrosis, which were more pronounced in the hepatocytes of mothers than in those of their suckling pups.


[Professional fatigue: a review of literature and implications for nurses].
The objective of this paper is to present literature revision of the factors which contribute to the professional hospital nurse fatigue. Burnout Syndrome, which is specific of the professionals who work directly with clients, like the hospital nurses, was chosen as a focus of study. The Burnout Syndrome is characterized by three fundamental symptoms: the sentiment of emotional fatigue, personal withdrawal and the reduction of professional achievement. In addition, the main associate variables were studied, and grouped in three categories: personal, organization and the work structure variables.


Circadian control of isoprene emissions from oil palm (Elaeis guineensis).
The emission of isoprene from the biosphere to the atmosphere has a profound effect on the Earth's atmospheric system. Until now, it has been assumed that the primary short-term controls on isoprene emission are photosynthetically active radiation and temperature. Here we show that isoprene emissions from a tropical tree (oil palm, Elaeis guineensis) are under strong circadian control, and that the circadian clock is potentially able to gate light-induced isoprene emissions. These rhythms are robustly temperature compensated with isoprene emissions still under circadian control at 38 degrees C. This is well beyond the acknowledged temperature range of all previously described circadian phenomena in plants. Furthermore, rhythmic expression of LHY/CCA1, a genetic component of the central clock in Arabidopsis thaliana, is still maintained at these elevated temperatures in oil palm. Maintenance of the CCA1/LHY-TOC1 molecular oscillator at these temperatures in oil palm allows for the possibility that this system is involved in the control of isoprene emission rhythms. This study contradicts the accepted theory that isoprene emissions are primarily light-induced.


Origin and organ-specific bioaccumulation pattern of perfluorinated alkyl substances in crabs.
Consumption of seafood is a major contributor to perfluorinated alkyl substances (PFASs) exposure. Crabs contain high levels of PFASs, and different PFASs are concentrated in their tissues depending on their habitat. Despite South Korea importing huge quantities of crabs, no investigation has been conducted on the effect of PFAS exposure. This study investigated the risk of exposure to PFASs when ingesting crabs. To determine the risk of exposure, 19 different PFAS species were measured in the edible parts (body, legs, offal, and eggs) of crabs originating from South Korea (n = 17), China (n = 14), India (n = 7), and Pakistan (n = 31), which were distributed in the fish markets of South Korea. The results revealed that, in contrast to short-chain PFASs, long-chain PFASs (PFCAs≥8, PFSAs≥6, and perfluorooactane sulfonamidoacetic acids (FOSAAs)≥8) were detected in crab samples from all four countries of origin, and in all the edible parts except for the legs. Perfluorooctanoic acid (PFOA; 16.9 ng/g in South Korea, 9.42 ng/g in China) and perfluoro-n-tridecanoic acid (PFTrDA; 5.35 ng/g in South Korea, 2.40 ng/g in China) were the predominant perfluoroalkyl carboxylic acids (PFCAs) detected in the crabs originating from South Korea and China, and perfluorooctane sulfonic acid (PFOS; 7.02 ng/g in Pakistan, 5.88 ng/g in India) was the predominant perfluoroalkyl sulfonic acids (PFSAs) detected in crabs originating from Pakistan and India. These results indicate that PFASs that are accumulated in crabs differ depending on the ocean from which they originate. The concentrations of PFOA and PFOS were significantly higher in the eggs and offal than in the legs and body of the crab. The average daily intake of PFOA and PFOS in South Koreans ranges from 0.01% to 0.07% based on the tolerable daily intake of EFSA and MFDS. These results establish the PFAS profiles and risk assessment of crabs that are distributed in South Korea.


Scope and mechanism of allylic C-H amination of terminal alkenes by the palladium/PhI(OPiv)2 catalyst system: insights into the effect of naphthoquinone.
Palladium-catalyzed oxidative amination of unactivated alkyl olefins has been developed to produce linear (E)-allylimides with high regioselectivity. This highly efficient transformation of alkenes has been achieved by enhancing the reoxidation of palladium with the strong oxidant PhI(OPiv)(2). The present work also provides the first systematic analysis of the mechanism of the allylic C-H oxidative amination. It has been found that naphthoquinone (NQ) plays a vital role in promoting olefin coordination to the palladium catalyst: in the absence of NQ, the turnover-limiting step is olefin coordination to palladium catalyst; in the presence of NQ, the reaction involves a rapid equilibration to give a nitrogen-coordinated olefin-Pd(NQ) complex that undergoes turnover-limiting allylic C-H bond activation to generate a pi-allyl-Pd intermediate. This work provides valuable insights for further studies on the functionalization of unactivated olefins.


The use of laser in neurosurgery.
In the neurosurgical practice the laser can be considered an additional instrument to improve the conventional techniques, or even a new method of treatment of some cerebral lesions. The laser surgery requires the association of three laser sources in combination. The CO2 offers the possibility of a precise cutting and of shrinking by vaporization which makes the removal of the lesion more complete without touching the surrounding areas. Nd:YAG is particularly suitable for tumor surgery allowing a deeper destruction with predictable effects associated with a more complete hemostasis. The combination Nd:YAG-Argon has clear indications for coagulation. The laser is very useful in high risk cases and in combination with the operating microscope in a restricted field near the critical areas of the brain and in the spinal cord. The association Argon-Nd: YAG is a new method for coagulation. In all cases of AAV malformation a complete exclusion was obtained and in 2 cases out of 7 reduced damage were registered. In saccular aneurysm in no case additional damage was registered, reduced damage was noticed in 2 out of 5 cases.