Prognostic Impact of Segmental Wall Motion Abnormality in Patients With Idiopathic Dilated Cardiomyopathy.
The clinical impact of left ventricular (LV) segmental wall motion abnormalities (SWMA) in patients with idiopathic dilated cardiomyopathy (IDCM) has not been well elucidated.Among 100 consecutive IDCM patients with follow-up visits, we enrolled 85 after excluding those with left bundle branch block and/or ventricular pacemaker implantation. LV wall motion was assessed using left ventriculography scored for 7 segments according to the American Heart Association classification as follows: 0, normokinesis; 1, hypokinesis; 2, akinesis; and 3, dyskinesis. SWMA were defined as a score dispersion of more than 1 degree among the segments.SWMA was exhibited by 26 patients. Kaplan-Meier curves demonstrated that the patients with SWMA (SWMA+) had a significantly higher cardiac event-free rate than the patients without SWMA (P < 0.001). Cox proportional hazards analysis showed that SWMA+ was an independent predictor of cardiac events (P = 0.03; hazard ratio = 3.38; 95% confidence interval [CI], 1.11-10.8). Furthermore, multiple regression analysis showed that SWMA+ was an independent predictor of decreased LV end-systolic dimension index after optimal pharmacotherapy (β = -0.24; 95%CI, -9.12 to -0.73; P = 0.02).SWMA is common in patients with IDCM and is independently associated with a poor prognosis and less morphometric and functional improvement of LV in response to pharmacotherapy.


Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand.
Starting from the observation that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L protein is expressed in both malignant and inflammatory cells in some highly vascularized soft tissue sarcomas, the angiogenic potential of TRAIL was investigated in a series of in vitro assays. Recombinant soluble TRAIL induced endothelial cell migration and vessel tube formation to a degree comparable to vascular endothelial growth factor (VEGF), one of the best-characterized angiogenic factors. However, the proangiogenic activity of TRAIL was not mediated by endogenous expression of VEGF. Although TRAIL potentiated VEGF-induced extracellular signal-regulated kinase (ERK) phosphorylation and endothelial cell proliferation, the combination of TRAIL + VEGF did not show additive effects with respect to VEGF alone in inducing vessel tube formation. Thus, although TRAIL has gained attention as a potential anticancer therapeutic for its ability to induce apoptosis in a variety of cancer cells, our present data suggest that TRAIL might also play an unexpected role in promoting angiogenesis, which might have therapeutic implications.


The engymetric determination of acute functional impairment in kidney graft function caused by cyclosporine A.
Engymetry offers a new means of continuously measuring nuclear radiation fields without any need of restricting the patient's mobility. In this study, kidney function was measured simultaneously and continuously for 6.6 h with engymetry, after application of a 12 h therapy dose of Cyclosporine A (CsA) of 4.0 +/- 1.8 mg per kg bodyweight (bw). 15 kidney transplanted patients participated in this study. 370 MBq 99Tcm-DTPA and 10 MBq 131I-OIH were injected during routine transplant scintigraphy. Renal function was monitored from the external disappearance curves of the tracers recorded by portable double radionuclide detectors. Renal impairment could be seen in the rising phase of CsA or coincided with the CsA maximum in 13 of the 15 patients. Under the impairment the half-life of 99Tcm-DTPA increased from 4.1 +/- 1.2 to 15.9 +/- 12.3 h (p less than 0.005) for 61 +/- 45 min and the half-life of 131I-OIH increased from 3.2 +/- 0.7 to 12.7 +/- 8.4 h (p less than 0.001) for 71 +/- 37 min. With noninvasive engymetry it is possible to detect renal functional impairment during long observation periods. Acute restriction in glomerular filtration and renal blood flow was discovered in human kidney graft recipients after the application of a low therapeutic CsA dose.


Morphoproteomics Identifies SIRT1 and EZH2 Pathways as Commonalities in B-cell Acute Lymphoblastic Leukemia: Pathogenetic Implications and Opportunities for Therapeutic Intervention.
B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic testing has revealed either no identifiable cytogenetic and genomic abnormalities in such patients or a wide range of aberrations that may or may not contribute to the block in differentiation and the associated proliferation of the malignant lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics to a representative spectrum of cases of newly diagnosed B-cell ALL in order to identify pathways that are known to be associated with the maintenance of the undifferentiated state while promoting proliferation. Our results showed nuclear expression in a majority of the lymphoblasts from bone marrow clot preparations of each of the study cases for both silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+ histone deacetylase and enhancer of Zeste homolog 2 (EZH2), a histone methyltransferase. These represent pathogenetic pathways capable of blocking differentiation and promoting proliferation of the B-cell ALL lymphoblasts. Data mining of the National Library of Medicine's MEDLINE Database and Ingenuity Pathway analysis revealed agents of relatively low toxicity-melatonin, metformin, curcumin and sulforaphane-that are capable of inhibiting directly or pharmacogenomically one or both of the SIRT1 and EZH2 pathways and should, in a combinatorial fashion, remove the block in differentiation and decrease the proliferation of the B-cell ALL lymphoblasts.


Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development.
The autonomic nervous system (cANS) is essential for proper heart function, and complications such as heart failure, arrhythmias and even sudden cardiac death are associated with an altered cANS function. A changed innervation state may underlie (part of) the atrial and ventricular arrhythmias observed after myocardial infarction. In other cardiac diseases, such as congenital heart disease, autonomic dysfunction may be related to disease outcome. This is also the case after heart transplantation, when the heart is denervated. Interest in the origin of the autonomic nerve system has renewed since the role of autonomic function in disease progression was recognized, and some plasticity in autonomic regeneration is evident. As with many pathological processes, autonomic dysfunction based on pathological innervation may be a partial recapitulation of the early development of innervation. As such, insight into the development of cardiac innervation and an understanding of the cellular background contributing to cardiac innervation during different phases of development is required. This review describes the development of the cANS and focuses on the cellular contributions, either directly by delivering cells or indirectly by secretion of necessary factors or cell-derivatives.


Microsurgical scalp reconstruction in the patient with cancer.
The literature regarding reconstruction of large scalp wounds with free tissue transfer consists mostly of case reports and small series, and none of the published reports focus on the particular problems of the oncology patient. Here the authors describe their experience with 37 flaps in 32 patients, all of whom required scalp reconstruction with free tissue transfer after tumor extirpation. Twenty-seven free flaps were performed at the time of the initial surgery and 10 were performed after a prior reconstruction failed. The authors describe the characteristics of the patients and procedures, including tumor type, wound size and complexity, flaps and recipient vessels used, preoperative and postoperative radiation therapy, and complications. Most (72 percent) of the tumors were recurrent or persistent. The free tissue transfer was successful in all patients. There was a 59 percent overall complication rate with 32 percent of patients requiring a secondary surgical procedure. Most of the complications were wound-healing complications. Although there were two cases of vein thrombosis, these were salvaged by revision, and no flaps were lost. Nine patients underwent postoperative radiation therapy that was well tolerated. Only four patients underwent cranioplasty at the time of the initial operation, and no secondary cranial reconstructions were performed. The authors conclude that preoperative and postoperative radiation therapies as well as the need for expedient tumor resection and immediate flap coverage are issues that make free tissue transfer attractive for the oncology patient who needs scalp reconstruction. Although the complication rate is relatively high and a significant percentage of patients require a secondary procedure, free flap coverage was efficacious for all patients in this group. Cranioplasty is not usually required but, if needed, alloplastic or autologous cranial reconstruction does not appreciably increase morbidity in the selected patient.


Transgenic copper/zinc superoxide dismutase modulates susceptibility to type I diabetes.
A growing body of evidence suggests that active oxygen is an important participant in the destruction of the pancreatic beta cell, which, in turn, leads to type I or insulin-dependent diabetes mellitus. Consequently, genetic factors predisposing susceptibility to insulin-dependent diabetes mellitus may include those that determine active oxygen metabolism. A direct test of this hypothesis is provided by a transgenic model for increased activity of Cu/Zn superoxide dismutase (EC 22.214.171.124), a principal radical scavenging enzyme. Here we demonstrate that elevated levels of this enzyme provided by a Cu/Zn superoxide dismutase transgene enhance the tolerance of pancreatic beta cells to oxidative stress-induced diabetogenesis. These results show that this transgenic approach holds promise for revealing the role of reactive oxygen in autoimmune models of diabetogenesis as well as in other models of disease pathology in which active oxygen has been implicated.


Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells.
During cortical development, N-methyl D-aspartate (NMDA) receptors are highly involved in neuronal maturation and synapse establishment. Their implication in the phenomenon of excitotoxicity has been extensively described in several neurodegenerative diseases due to the permissive entry of Ca2+ ions and massive accumulation in the intracellular compartment, which is highly toxic to cells. Ionising radiation is also a source of stress to the cells, particularly immature neurons. Their capacity to induce cell death has been described for various cell types either by directly damaging the DNA or indirectly through the generation of reactive oxygen species responsible for the activation of a battery of stress response effectors leading in certain cases, to cell death. In this study, in order to determine whether a link exists between NMDA receptors-mediated excitotoxicity and radiation-induced cell death, we evaluated radiation-induced cell death in vitro and in vivo in maturing neurons during the fetal period. Cell death induction was assessed by TUNEL, caspase-3 activity and DNA ladder assays, with or without the administration of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist which blocks neuronal Ca2+ influx. To further investigate the possible involvement of Ca2+-dependent enzyme activation, known to occur at high Ca2+ concentrations, we examined the protective effect of a calpain inhibitor on cell death induced by radiation. Doses ranging from 0.2 to 0.6 Gy of X-rays elicited a clear apoptotic response that was prevented by the injection of dizocilpine (MK-801) or calpain inhibitor. These data demonstrate the involvement of NMDA receptors in radiation-induced neuronal death by the activation of downstream effectors, including calpain-related pathways. An increased apoptotic process elicited by radiation, occurring independently of the normal developmental scheme, may eliminate post-mitotic but immature neuronal cells and deeply impair the establishment of the neuronal network, which in the case of cortical development is critical for cognitive capacities.


High-pressure neurological syndrome (HPNS).
High-pressure neurological syndrome (HPNS) is a condition encountered in diving beyond a depth of 100 m. Manifestations include headache, tremor, myoclonus, neuropsychiatric disturbances and EEG changes. Convulsions are seen only in experimental animals. Most of the changes are reversible on surfacing but some such as memory disturbances may linger on for long periods. Excessive atmospheric pressure is the most important factor in the pathogenesis of HPNS. Neurotransmitter changes occur of which serotonin appears to be a more likely mediator because of the resemblance of HPNS to serotonin syndrome. Anesthetics and anticonvulsants have been used in experimental animals but are unsuitable for use in human divers. Breathing gas mixtures such as heliox have enabled the extension of depth of diving without HPNS. Use of 5-HT1A receptor antagonists may provide an interesting approach to prevention of HPNS.


Use of profession-role exchange in an interprofessional student team-based community health service-learning experience.
During interprofessional clinical practice, compared to understanding of one's own professional role and function, it might be more difficult to clarify the roles and contributions of the other health-care team members because of the inter-professional barrier. In order to provide students the opportunity for real experience with other professions in team environments and enhance their perceptions of other professions' roles, this study developed a comprehensive and multi-dimension extracurricular interprofessional education (IPE) model through designing and integrating a profession-role exchange component, that was medical students as pharmacists or nurses, pharmacy students as physicians or nurses, and nursing students as physicians or pharmacists in the interprofessional health-care student team, into the service learning experience in a real community setting. In this pre/post-intervention study, the effect of integrated profession-role exchange experiences on the students' attitudes towards interprofessional collaboration and their role clarification was evaluated among 60 student volunteers (20 medical students, 20 pharmacy students and 20 nursing students). All involved students were divided into the profession-role exchange intervention group and the control group. Subjects in the control group did not participate the profession-role exchange experiences, the other IPE procedures were the same for both groups. Three survey instruments for attitudes toward interprofessional clinical collaboration were respectively used to measure the students' attitudes toward physician-pharmacist, physician-nurse and nurse-pharmacist collaborations. "Roles and responsibilities" subscale of Readiness for Interprofessional Learning Scale was used to evaluate the overall role clarification during IPE. Compared to the control IPE activity, the addition of profession-role exchange component resulted in the significant increase in students' positive attitudes towards interprofessional collaboration, and the enhancement of students' role awareness. The profession-role exchange might be more effective and better initiate students to the practice of interprofessional collaboration, and could be used as an effective IPE tool for improving the role awareness of health-care students.


Commonly conserved genetic fragments revealed by genome profiling can serve as tracers of evolution.
We developed a method to produce, identify and analyze DNA fragments for the purpose of taxonomic classification. Genome profiling (GP) is a strategy that identifies genomic DNA fragments common to closely related species without prior knowledge of the DNA sequence. Random PCR, one of the key technologies of GP, is used to produce fragments and may be used even when there are mutations at the priming site. These fragments can then be distinguished based on the information of mobility and melting pattern when subjected to temperature gradient gel electrophoresis (TGGE). Corresponding fragments among several species, designated as commonly conserved genetic fragments (CCGFs), likely have the same genetic origin or correspond to the same gene. The criteria for identification of CCGFs has been defined and presented here. To assess this prediction, some of the fragments were sequenced and were confirmed to be CCGFs. We show that genome profiles bearing evolutionarily conserved CCGFs can be used to classify organisms and trace evolutionary pathways, among other profound applications.


Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma.
Despite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated.


Dynamics of thrombophlebitis in central venous catheterization via basilic and cephalic veins.
The incidence distribution of thrombophlebitis after central catheterization via basilic and cephalic veins was investigated, using 227 catheters made of various plain or heparin-coated materials and with differing stiffness and surface structures. The platelet-adhesion stimulating properties were measured in vitro. Thrombophlebitis showed similar incidence patterns with all catheter types. The maximum incidence of venous reaction was found one to ten days after catheter insertion (central tendency 3-8 days with a peak at 5 days). After ten days the risk of thrombophlebitis fell significantly. The results supported the view that central venous catheters inserted via basilic or cephalic veins should not be withdrawn or exchanged as prophylaxis against thrombophlebitis, at any rate when long-term catheterization is intended. For conclusive comparisons between catheter materials regarding induction of clinically apparent thrombophlebitis, all the patients in the trial should be catheterized for ten days or more, unless symptoms of venous reaction arise earlier.


Antiproliferative activity of the topoisomerase I inhibitors topotecan and camptothecin, on sub- and postconfluent tumor cell cultures.
We have assessed the antiproliferative effects of a 24-hr exposure to the topoisomerase I inhibitors, topotecan and camptothecin, on two colon and one ovarian human tumor cell lines, cultured as subconfluent and as multilayered postconfluent cultures. Chemosensitivity was measured by the sulforhodamine B assay. In general, postconfluent cultures were less sensitive to these agents, yielding GI50S (drug concentrations inhibiting growth by 50%) from 1.2 to more than 6000 times higher than those of subconfluent cultures. Both compounds displayed similar effects on subconfluent cells, inducing complete growth inhibition at concentrations ranging from 0.03 to 0.5 microM. Topotecan, however, was more potent than camptothecin in two out of the three cell lines tested as multilayered postconfluent cultures. Topoisomerase I mRNA expression on postconfluent cultures was 50% lower than on subconfluent cultures in the three cell lines studied. However, we did not detect any reproducible differences in topoisomerase I protein expression and in relaxation activity of supercoiled DNA between the two types of cultures. From accumulation experiments it appeared that the peak concentration of the lactone form of topotecan as well as the area under the concentration-time curve (AUC) were 2-fold higher in the monolayer than in the multilayer cultures. Therefore, the differences in the activity of topoisomerase I inhibitors under our experimental conditions were likely due to a decreased rate of proliferation of postconfluent cells, associated with a reduction in drug uptake.


Nostril-specific and structure-based olfactory learning of chiral discrimination in human adults.
Practice makes perfect. In human olfaction, such plasticity is generally assumed to occur at the level of cortical synthetic processing that shares information from both nostrils. Here we present findings that challenge this view. In two experiments, we trained human adults unirhinally for the discrimination between odor enantiomers over a course of about 10 to 11 days. Results showed that training-induced perceptual gain was restricted to the trained nostril yet partially generalized to untrained odor enantiomers in a structure- rather than quality- based manner. In other words, learning enhanced the differentiation of chirality (molecular configuration) as opposed to overall odor quality (odor object) per se. These findings argue that, unlike earlier beliefs, one nostril does not readily know what the other learns. Moreover, the initial analytical processing of the structural features of uninarial olfactory input remains plastic in human adults.


Nanostructured silicon based thin film transistors processed in the plasma dark region.
Nanostructured silicon (na-Si:H) thin films were fabricated using plasma enhanced chemical vapour deposition (PECVD) technique under high silane hydrogen dilution and a discharge frequency of 27 MHz, where the substrate was located in the dark region of the plasma, protected by a grounded metal grid. By not exposing the growth surface directly to the plasma we avoid the silicon growth surface to sustain a high ion bombardment leading to a less defective surface and highly compact films. The intrinsic films grown under these conditions were used to produce the channel region of thin film transistors (TFTs) with a bottom gate staggered configuration, integrating different dielectric layers. The devices produced exhibit a field effect mobility close to 1.84 cm2 V(-1) s(-1), threshold voltage around 2 V, on/off ratio above 10(7) and sub-threshold slope below 0.5 V/decade, depending on the dielectric used.


Effect of Pterygium Morphology on Recurrence with Preoperative Subconjunctival Injection of Mitomycin-C in Primary Pterygium Surgery.
To investigate the effect of pterygium morphology on recurrence with preoperative subconjunctival injection of mitomycin-C in primary pterygium surgery. Quasi-experimental study. Eye Department, Combined Military Hospital, Malir Cantt, Karachi, from February 2017 to February 2018. On the basis of pterygium morphology, 165 eyes of 165 patients were equally divided into three equal groups of atrophic, intermediate and fleshy pterygia. In each morphology group, length was graded into three groups using limbus, pupil margin and midiris as landmarks. All pterygia received 0.1 ml of mitomycin-C injection in a concentration of 0.15 mg/ml at 24 hours prior to undergoing a bare sclera surgical excision technique in all cases. All patients were followed up for 12 months. The recurrence rate was recorded in each morphology group. Pearson Chi-Square test was used to compare recurrence rate and morphology group. Fisher's exact test was applied to compare recurrence rate with length and age in each type of morphology. Among the three morphology groups, the recurrence rate was statistically significant between fleshy and atrophic pterygia (p=0.01) and no significant association was found among other morphology comparisons. Age less than 40 years had a significant effect on recurrence in all morphology groups. Length did not affect the recurrence rate in any of morphology types. Recurrence of primary pterygium is related to fleshiness of the pterygium and is a significant risk factor for recurrence after preoperative subconjunctival injection of mitomycin-C given at 24 hours before sclera excision.


Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.
Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).


Ionic radii of hydrated sodium cation from QTAIM.
The sodium cation is ubiquitous in aqueous chemistry and biological systems. Yet, in spite of numerous studies, the (average) distance between the sodium cation and its water ligands, and the corresponding ionic radii, are still controversial. Recent experimental values in solution are notably smaller than those from previous X-ray studies and ab initio molecular dynamics. Here we adopt a "bottom-up" approach of obtaining these distances from quantum chemistry calculations [full MP2 with the 6-31++G(d,p) and cc-pVTZ basis-sets] of gas-phase Na+(H2O)n clusters, as a function of the sodium coordination number (CN = 2-6). The bulk limit is obtained by the polarizable continuum model, which acts to increase the interatomic distances at small CN, but has a diminishing effect as the CN increases. This extends the CN dependence of the sodium-water distances from crystal structures (CN = 4-12) to lower CN values, revealing a switch between two power laws, having a small exponent at small CNs and a larger one at large CNs. We utilize Bader's theory of atoms in molecules to bisect the Na+-O distances into Na+ and water radii. Contrary to common wisdom, the water radius is not constant, decreasing even more than that of Na+ as the CN decreases. We also find that the electron density at the bond critical point increases exponentially as the sodium radius decreases.


Differences in the structure and dynamics of the apo- and palmitate-ligated forms of Aedes aegypti sterol carrier protein 2 (AeSCP-2).
Sterol carrier protein-2 (SCP-2) is a nonspecific lipid-binding protein expressed ubiquitously in most organisms. Knockdown of SCP-2 expression in mosquitoes has been shown to result in high mortality in developing adults and significantly lowered fertility. Thus, it is of interest to determine the structure of mosquito SCP-2 and to identify its mechanism of lipid binding. We report here high quality three-dimensional solution structures of SCP-2 from Aedes aegypti determined by NMR spectroscopy in its ligand-free state (AeSCP-2) and in complex with palmitate. Both structures have a similar mixed alpha/beta fold consisting of a five-stranded beta-sheet and four alpha-helices arranged on one side of the beta-sheet. Ligand-free AeSCP-2 exhibited regions of structural heterogeneity, as evidenced by multiple two-dimensional (15)N heteronuclear single-quantum coherence peaks for certain amino acids; this heterogeneity disappeared upon complex formation with palmitate. The binding of palmitate to AeSCP-2 was found to decrease the backbone mobility of the protein but not to alter its secondary structure. Complex formation is accompanied by chemical shift differences and a loss of mobility for residues in the loop between helix alphaI and strand betaA. The structural differences between the alphaI and betaA of the mosquito and the vertebrate SCP-2s may explain the differential specificity (insect versus vertebrate) of chemical inhibitors of the mosquito SCP-2.


Diagnostic radiology in wartime.
During the Lebanon War, 1982, over 80% of the wounded were sent from the triage area of the hospital directly to the radiology department. This article reports changes in the working pattern and organization of the department that were instituted for emergency treatment in wartime, and describes radiological examination methods for different organs. Computerized tomography is emerging as the most important diagnostic tool in addition to conventional radiological examinations.


Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products.
Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned. We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study. Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods.


Perceptual Training Restores Impaired Cortical Temporal Processing Due to Lead Exposure.
Low-level lead exposure is a risk factor for cognitive and learning disabilities in children and has been specifically associated with deficits in auditory temporal processing that impair aural language and reading abilities. Here, we show that rats exposed to low levels of lead in early life display a significant behavioral impairment in an auditory temporal rate discrimination task. Lead exposure also results in a degradation of the neuronal repetition-rate following capacity and response synchronization in primary auditory cortex. A modified go/no-go repetition-rate discrimination task applied in adult animals for ∼50 days nearly restores to normal these lead-induced deficits in cortical temporal fidelity. Cortical expressions of parvalbumin, brain-derived neurotrophic factor, and NMDA receptor subunits NR2a and NR2b, which are down-regulated in lead-exposed animals, are also partially reversed with training. These studies in an animal model identify the primary auditory cortex as a novel target for low-level lead exposure and demonstrate that perceptual training can ameliorate lead-induced deficits in cortical discrimination between sound sequences.


Is Preemptive Kidney Transplantation Associated With Improved Outcomes when Compared to Non-preemptive Kidney Transplantation in Children? A Systematic Review and Meta-Analysis.
Main Problem: Preemptive kidney transplantation (PKT) is performed prior to dialysis initiation to avoid dialysis-related morbidity and mortality in children and adolescents. We undertook a systematic review to compare clinical outcomes in PKT versus kidney transplantation after dialysis initiation in paediatric patients. Methods: The bibliographic search identified studies that compared paediatric recipients of a first or subsequent, living or deceased donor PKT versus non-preemptive kidney transplant. Methodological quality was assessed for all studies. Data were pooled using the random-effects model. Results: Twenty-two studies (n = 22,622) were included. PKT reduced the risk of overall graft loss (relative risk (RR) .57, 95% CI: .49-.66) and acute rejection (RR: .81, 95% CI: .75-.88) compared to transplantation after dialysis. Although no significant difference was observed in overall patient mortality, the risk of patient death was found to be significantly lower in PKT patients with living donor transplants (RR: .53, 95% CI: .34-.83). No significant difference was observed in the incidence of delayed graft function. Conclusion: Evidence from observational studies suggests that PKT is associated with a reduction in the risk of acute rejection and graft loss. Efforts should be made to promote and improve rates of PKT in this group of patients (PROSPERO). Systematic Review Registration: https://clinicaltrials.gov/, CRD42014010565.


Analytic energy gradients in closed-shell coupled-cluster theory with spin-orbit coupling.
Gradients in closed-shell coupled-cluster (CC) theory with spin-orbit coupling included in the post Hartree-Fock treatment have been implemented at the CC singles and doubles (CCSD) level and at the CCSD level augmented by a perturbative treatment of triple excitations [CCSD(T)]. The additional computational effort required in analytic energy-gradient calculations is roughly the same as that for ground-state energy calculations in the case of CCSD, and it is about twice in the case of CCSD(T) calculations. The structures, harmonic frequencies, and dipole moments of some heavy-element compounds have been calculated using the present analytic energy-gradient techniques including spin-orbit coupling. The results show that spin-orbit coupling can have a significant influence on both the equilibrium structure and the harmonic vibrational frequencies and that its inclusion is essential to obtain reliable and accurate estimates for geometrical parameters of heavy-element compounds.


Vibrational control of the reaction pathway in the H + CHD3 → H2 + CD3 reaction.
An accurate full-dimensional quantum state-to-state simulation of the six-atom title reaction based on first-principles theory is reported. Counterintuitive effects are found: Increasing the energy in the reactant's CD3 umbrella vibration reduces the energy in the corresponding product vibration. An in-depth analysis reveals the crucial role of the effective dynamical transition state: Its geometry is controlled by the vibrational states of the reactants and subsequently controls the quantum state distribution of the products. This finding enables generalizing the concept of transition state control of chemical reactions to the quantum state-specific level.


Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with Gram-positive respiratory pathogens.
A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of Streptococcus pneumoniae superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens: Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with Streptococcus pyogenes superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens.


Characterization of Low Pathogenic Avian Influenza Virus Subtype H9N2 Isolated from Free-Living Mynah Birds (Acridotheres tristis) in the Sultanate of Oman.
A low pathogenic avian influenza virus was identified from free-living birds (mynah, Acridotheres tristis) of the starling family. Virus was isolated by inoculation of homogenized suspension from lung, tracheal, spleen, and cloacal swabs into the allantoic cavity of embryonated chicken eggs. Subtype of the isolate was characterized as H9N2 by hemagglutination inhibition test using monospecific chicken antisera to a wide range of influenza reference strain. Pathogenicity of the isolate was determined by intravenous pathogenicity index. The virus was reisolated from experimentally infected chicken. Additionally, the isolate was subjected to reverse transcriptase PCR using partial hemagglutinin (HA) gene-specific primers and yielded an amplicon of 487 bp. HA gene sequence analysis revealed 99% sequence homology among mynah and chicken isolates from Oman. On phylogenetic analysis, isolates from mynah (A/mynnah/Oman/AIVS6/2005) and chicken (A/chicken/Oman/AIVS3/2006; A/chicken/Oman/AIVS7/2006) clustered together tightly, indicating these free-flying birds may be a source of introduction of H9N2 subtype in poultry bird in Oman. Moreover, the HA gene of H9N2 isolates from Oman resembled those of viruses of the G1-like lineage and were very similar to those from United Arab Emirates.


Knowledge is power: using nursing information management and leadership interventions to improve services to patients, clients and users.
This paper examines the purpose, role and function of information and information management within health care today. It is set within the context of a specialist forensic learning disability setting. Changes in politics, government legislation and reforms of the National Health Service (NHS) have created a need to equip managers with the necessary tools and skills to be able to lead and manage effectively. As such there has been a great emphasis upon specialist training, such as the government-driven Leading an Empowered Organisation courses, for nurse managers and nurses with leadership potential. Yet with the drive to generate a new wave culture within the NHS of inspirational leaders, are we still overlooking a critical and key area which is fundamental in achieving and delivering cost effective, quality health care--the area of information management within health care today? The processes presented in this paper are structured through a strategic nursing management and leadership performance implementation model, the Clinical Nursing Leadership Learning and Action Process (CLINLAP) model, which facilitates work-based learning and capability development in the reality of everyday clinical activities. Through the model, the emphasis is to make clinical goals specific, roles explicit, processes clear and encourage these activities to be carried out within an environment of open relationships. The use of CLINLAP model assisted as a management and leadership technology to manage change in the workplace so as to improve services to patients in Yelday Lodge. Structured management and leadership interventions led to observable positive change in information management on Yelday Lodge. The conclusion is that sustained quality information could be embedded in nursing practice at Yelday Lodge or elsewhere by evaluating and discussing the different information management approaches within the practice area through the use of structured management and leadership interventions. The use of the CLINLAP model is recommended for use as a model for managing information, knowledge and communication for results within nursing and health care services.


Design and Performance Analysis of a Constellation of Nanosatellites to Monitor Water Quality in the Southern Catchment of the Baltic Sea.
The quality of inland waters has a significant influence on human life and the functioning of the environment. The disasters that result from water pollution may cause major financial losses and lead to irreversible changes in the ecosystem, such as the dying out of endemic species of plants and animals. Quick detection of pollution sources may minimise those negative effects and reduce the costs of their elimination. The study presents a constellation design that provides imagery in the optic range and that might supplement the point water quality measurements that are conducted in situ. The area of interest was the southern catchment of the Baltic Sea and the main rivers in the region. The requirements for the designed mission were defined in reference to the remote sensing needs concerning the monitoring of water quality, the characteristics of the analysed area, and weather conditions. Based on these requirements, the Simera Sense MultiScape100 CIS sensor and the M6P nanosatellite manufactured by NanoAvionics were selected. The authors proposed a process for selecting the optimum orbit, taking into account the area of interest, the possibilities of the satellite platform, and of the sensor's optics. As a result of the analyses, four concepts of creating a constellation were presented. Each constellation consisted of four nanosatellites. The designs were then subjected to performance analysis, considering the lighting limitations. Among the proposed systems, the constellation designed by the authors was distinguished; it used four orbital planes and achieved the coverage and availability of imagery in the time that was best suited to monitoring the waters. Thanks to a small number of platforms, the costs of the mission are relatively low, and it might significantly improve awareness of the current state of surface waters in the southern catchment of the Baltic Sea.


Biological and environmental factors associated with risk of schistosomiasis mansoni transmission in Porto de Galinhas, Pernambuco State, Brazil.
Schistosomiasis has expanded to the coast of Pernambuco State, Brazil, where there are frequent reports of Biomphalaria glabrata snails and human cases of the disease. This study analyzes factors related to schistosomiasis transmission risk in Porto de Galinhas. A one-year malacological survey was conducted to identify biological, abiotic, and environmental factors related to the host snail breeding sites. Data analysis used Excel 2010, GTM Pro, and ArcGis 10. A total of 11,012 B. glabrata snails were captured in 36 breeding sites, and 11 schistosomiasis transmission foci were identified. A negative correlation was found between breeding site temperature and snail density and infection rate, and a positive correlation with pH and salinity. The rainy season showed a positive correlation with snail density and infection rate. The study emphasizes the factors involved in the maintenance of schistosomiasis breeding sites, in light of persistence of this disease in Porto de Galinhas for more than 10 years.


Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor.
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B-cell lymphoma cells harboring gain-of-function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications.


Nutrient Acquisition and the Metabolic Potential of Photoferrotrophic Chlorobi.
Anoxygenic photosynthesis evolved prior to oxygenic photosynthesis and harnessed energy from sunlight to support biomass production on the early Earth. Models that consider the availability of electron donors predict that anoxygenic photosynthesis using Fe(II), known as photoferrotrophy, would have supported most global primary production before the proliferation of oxygenic phototrophs at approximately 2.3 billion years ago. These photoferrotrophs have also been implicated in the deposition of banded iron formations, the world's largest sedimentary iron ore deposits that formed mostly in late Archean and early Proterozoic Eons. In this work we present new data and analyses that illuminate the metabolic capacity of photoferrotrophy in the phylum Chlorobi. Our laboratory growth experiments and biochemical analyses demonstrate that photoferrotrophic Chlorobi are capable of assimilatory sulfate reduction and nitrogen fixation under sulfate and nitrogen limiting conditions, respectively. Furthermore, the evolutionary histories of key enzymes in both sulfur (CysH and CysD) and nitrogen fixation (NifDKH) pathways are convoluted; protein phylogenies, however, suggest that early Chlorobi could have had the capacity to assimilate sulfur and fix nitrogen. We argue, then, that the capacity for photoferrotrophic Chlorobi to acquire these key nutrients enabled them to support primary production and underpin global biogeochemical cycles in the Precambrian.


Tracking the Origin and Deciphering the Phylogenetic Relationship of Porcine Epidemic Diarrhea Virus in Ecuador.
In 2010, new Chinese strains of porcine epidemic diarrhea virus (PEDV), clinically more severe than the classical strains, emerged. These strains were spread to United States in 2013 through an intercontinental transmission from China with further spreading across the world, evidencing the emergent nature of these strains. In the present study, an analysis of PEDV field sequences from Ecuador was conducted by comparing all the PEDV S gene sequences available in the GenBank database. Phylogenetic comparisons and Bayesian phylogeographic inference based on complete S gene sequences were also conducted to track the origin and putative route of PEDV. The sequence from the PED-outbreak in Ecuador was grouped into the clade II of PEDV genogroup 2a together with other sequences of isolates from Mexico, Canada, and United States. The phylogeographic study revealed the emergence of the Chinese PEDV strains, followed by spreading to US in 2013, from US to Korea, and later the introduction of PEDV to Canada, Mexico, and Ecuador directly from the US. The sources of imports of live swine in Ecuador in 2014 were mainly from Chile and US. Thus, this movement of pigs is suggested as the main way for introducing PEDV to Ecuador.


Development of antibacterial resistance: the Dutch experience.
An ongoing registration of resistance patterns of microorganisms in a large area in the Netherlands demonstrated a slow but steady increase of resistance to several antibacterials in the past ten years. For some bacteria and for some selected antimicrobial agents this increase was such that it might no longer be justifiable to choose them for empirical therapy. For Escherichia coli, resistance increased from 14% in 1982 to 28% in 1992 for co-trimoxazole and for trimethoprim and from 24% to 34% for amoxycillin. For nitrofurantoin the figures were 1.5% and 4.0%, respectively. Comparison with other areas in the Netherlands showed similar results, so it can be considered a nationwide problem which may have consequences for national antibiotic guidelines for the treatment of infections.


[Transvaginal, ultrasound-controlled follicle puncture].
Between December 1986 and November 1987, 588 transvaginal sonographically-guided oocyte retrievals, using a vaginal transducer, were performed for in vitro fertilization at the University of Bonn. All follicles were accessible. No complication occurred except one case of pelviperitonitis in a patient with preoperatively diagnosed sactosalpinx. Because this technique is safe, non-invasive, and performable without general anaesthesia, we also retrieved eggs in patients despite poor hormonal values and endogenous LH-surge. In all, clinical pregnancies were diagnosed in 85 patients. Pregnancy rates per embryo transfer, oocyte retrieval and stimulated cycle, respectively were 19.0%, 14.5% and 12.0%. The advantages of the transvaginal technique, using a vaginal transducer compared with the laparoscopically-guided as well as with other sonographically-guided techniques of oocyte retrieval, are obvious (possibly without general anaesthesia, in general all follicles are accessible, very low complication rates, low discomfort to patient, and less amount of time and staff). Therefore, this technique seems to be the method of first choice. A laparoscopically-guided oocyte retrieval is only indicated, when a laparoscopic screening of pelvic organs or a gamete intrafallopian transfer are to be performed simultaneously.


Transverse formamide gradients as a simple and easy way to optimise DNA single-strand conformation polymorphism analysis.
Although widely used, the detection of DNA mutations by the single-strand conformation polymorphism (SSCP) method is often hampered by the need to examine a large set of electrophoretic conditions in order to select the one suited to the DNA sequence under study. We show here that the use of transverse chemical gradient gels allows for a quick and easy optimisation of SSCP analysis, as exemplified on two mutations in exon 2 of the alpha-1-antitrypsin gene.


[Comprehensive care program for the mentally ill in Spanish prisons (PAIEM): assessment after four years operation].
To assess the comprehensive care program for the mentally ill in prison (PAIEM), which has been implemented for 3 years in Spanish prisons with the aim of improving processes and results. Descriptive study of the data gathered from an anonymous questionnaire completed by members of the PAIEM team in prisons. Frequency distributions were obtained of all the variables relating to facts, attitudes, opinions, experiences, situations and processes of the PAIEM. 91.2% of the PAIEM teams responded. Psychologists, educators, doctors and social workers were the professionals that collaborated most actively in the PAIEM (73%-84%) and were the ones to act most frequently as tutors. The mentally ill are usually located in ordinary modules (80%). The most commonly used activities for their psycho-social rehabilitation are self care (73%), education for health, preparation for daily life and social skills (more than 60%). Interventions with families are basically by telephone (79%). Bivariate analysis showed that the PAIEMs that operate most effectively are those that coordinate well with other technical teams, that prepare referral more than six months prior to release and ones where the NGOs process the referrals. Over 71% of the professionals observed improvements of disabilities and needs in over half the patients more than half of the professionals involved are satisfied (3.4/5) with their participation, although they acknowledge that there is a greater work load. The activities of the PAIEM are adequate, especially in the phases of early detection, stabilisation and rehabilitation and less so in the social incorporation phase, which improves when the third sector intervenes in referrals of patients to the social health care network outside prison.


Higher prevalence of obsessive-compulsive symptoms in patients with blepharospasm than in patients with hemifacial spasm.
The prevalences of obsessive-compulsive symptoms in patients suffering from blepharospasm and in those with hemifacial spasm were determined. The two conditions have similar symptoms, but only blepharospasm is etiologically linked to basal ganglia dysfunction. After being interviewed with the Structured Clinical Interview for DSM-III-R, 13 patients with blepharospasm and 13 with hemifacial spasm completed the SCL-90-R and the Hamburg Obsession/Compulsion Inventory-Short Form. Patients in the blepharospasm group had significantly more obsessive-compulsive symptoms, as indicated by higher scores on the Hamburg Obsession/Compulsion Inventory-Short Form, than the patients with hemifacial spasm. SCL-90-R scores were in the normal range for nine and eight categories, respectively (out of nine). The findings provide additional support for the hypothesis that obsessive-compulsive symptoms are related to basal ganglia dysfunction.


A novel whole peanut butter refined by stirred media mill: The size, microstructure, rheology, nutrients, and flavor.
A novel whole peanut butter (PB) was developed using an emerging technology called stirred media mill (SMM). The impact of SMM on the size, microstructure, rheology, nutrient, and flavor of PB was investigated. The SMM treatment significantly decreased the particle size of PB, damaged cell structure, and released the oil body from cells. The apparent viscosity of PB decreased with the grinding process. Visual inspection revealed that the colloidal stability of PB was improved. The fatty acid composition was not affected by the grinding process. However, the tocopherol contents of the extracted oil slightly increased. Electronic nose and GC-MS analysis indicated that SMM could alter the flavor of PB after grinding for 45 min. Overall, SMM was a potential process technology to manufacture stable nut butter with smooth texture and delightful flavor profile.


Self-reported health and fitness habits of certified athletic trainers.
As health care providers, certified athletic trainers (ATs) should be role models for healthy behaviors. To analyze the self-reported health and fitness habits of ATs. A cross-sectional, cluster random sample. Online questionnaire. Of a sampling frame of 1000 potential participants, 275 ATs completed the questionnaire. Health habits and activity were based on a typical 7-day week. A total of 41% of the participants met the exercise recommendations of the American College of Sports Medicine; 7% reported being sedentary. Differences were noted between the sexes for fitness habits (P < .035) and composite health score (P < .001). None of the ATs reported meeting the Daily Reference Intake for all 5 food groups. Seven percent of female ATs consumed more alcohol than recommended, compared with 2% of males. However, 80% of males and 93% of females reported consuming 5 or fewer drinks per week. Only 0.8% reported currently smoking. This sample of ATs had better health and fitness habits than the general population but did not meet professional recommendations set forth by the American College of Sports Medicine or the United States Department of Agriculture. Thus, these ATs were not ideal role models in demonstrating healthy behaviors.


[Revascularization in Stable Ischemic Heart Disease: Whether to Change the Approach?]
Current international guidelines on stable ischemic heart disease (IHD) state that coronary revascularization is indicated in cases of: limiting ischemic symptoms while on optimal medical therapy (OMT); high risk coronary anatomy; high risk stress test result. At the same time, many results supporting these conclusions were obtained in relatively old studies, conducted when the approaches to medical therapy and revascularization techniques differed greatly from contemporary practice. Many of the conclusions have been based on data from observational studies and subanalyses of randomized clinical trials, therefore methodologically are not sufficiently reliable. Moreover, the results of more modern trials do not coincide with the older. This situation has generated contradictory opinions on the indications for coronary revascularization in patients with IHD in the cardiology community. This review contains analysis of the evidence base of current revascularization guidelines, data on components of OMT, and discussion of the need for large-scale randomized clinical trial comparing effectiveness of OMT and OMT+revascularization in patients with stable IHD.


Proteomic analysis of a Candida albicans pir32 null strain reveals proteins involved in adhesion, filamentation and virulence.
We have previously characterized Pir32, a Candia albicans cell wall protein that we found to be involved in filamentation, virulence, chitin deposition, and resistance to oxidative stress. Other than defining the cell shape, the cell wall is critical for the interaction with the surrounding environment and the point of contact and interaction with the host surface. In this study, we applied tandem mass spectrometry combined with bioinformatics to investigate cell wall proteome changes in a pir32 null strain. A total of 16 and 25 proteins were identified exclusively in the null mutant strains grown under non-filamentous and filamentous conditions. These proteins included members of the PGA family with various functions, lipase and the protease involved in virulence, superoxide dismutases required for resisting oxidative stress, alongside proteins required for cell wall remodeling and synthesis such as Ssr1, Xog1, Dfg5 and Dcw1. In addition proteins needed for filamentation like Cdc42, Ssu81 and Ucf1, and other virulence proteins such as Als3, Rbt5, and Csa2 were also detected. The detection of these proteins in the mutant and their lack of detection in the wild type can explain the differential phenotypes previously observed.


Severe and near-fatal anaphylactic reactions triggered by chlorhexidine-coated catheters in patients undergoing renal allograft surgery: a case series.
Although intraoperative anaphylaxis during surgery is a rare event, we describe five patients who experienced perioperative anaphylactic reactions during renal transplantation and were referred for investigation. Skin-prick and intradermal skin tests were done to investigate potential allergies to drugs given perioperatively prior to the development of anaphylaxis, including basiliximab, propofol, cefazolin, cis-atracurium, fentanyl, latex, remifentanil, and chlorhexidine. In addition, in vitro serologic testing for specific IgE was done in patients suspected to have had chlorhexidine anaphylaxis. All five patients were male, with a mean age of 48 yr (range 30-69). Skin testing for all drugs was non-reactive except for chlorhexidine, which was positive in four of five patients (one patient refused intradermal testing). In vitro test results for chlorhexidine-specific IgE were positive in all of the patients. Anesthetic records showed that intraoperative anaphylaxis had occurred immediately after insertion of a chlorhexidine-coated central venous catheter. Intraoperative insertion of chlorhexidine-coated central venous catheters can trigger life-threatening anaphylaxis in susceptible patients undergoing renal transplantation.


Randomized controlled trial of clopidogrel to prevent primary arteriovenous fistula failure in hemodialysis patients.
The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula (AVF). Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure. A double-blind, randomized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients. Ninety three patients were randomized to receive 75 mg/daily of clopidogrel or placebo. The treatment was initiated 7-10 days prior to scheduled access surgery and continued up to six weeks postoperatively, and then patients were monitored for six months. The primary outcome was AVF failure eight weeks after fistula creation. With a permuted block randomization schedule, 46 patients received clopidogrel and 47 patients received control placebo. The primary AVF failures at two months were 21.6% in placebo group and 5.2% in clopidogrel group (P = 0.03). The hazard ratio for the incidence of primary AVF failure was 0.72 (CI 95%, 0.41-1.01). Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration. First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group (P = 0.008). No life-threatening adverse event or severe bleeding was recorded in both groups. Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients.


Survival of low-birthweight infants in a Queensland provincial centre.
Survival figures over a five-year period of low-birthweight infants (2000 g or less at birth) in two intensive care nurseries in Rockhampton , Queensland, are presented. The units were level 2 nurseries with some level 3 amenities . All live-born infants born in Rockhampton and infants retrieved from outlying areas were included in the study. The survival rate was nil for infants of less than 501 g at birth, 40% for those weighing between 500 and 751 g, 45% for those weighing 750 to 1001 g, 85% for those weighing 1001 to 1501 g and 91% for those weighing 1500 to 2001 g at birth. These results compare favourably with those for some level 3 intensive-care units.


The ratio of circulating follicular T helper cell to follicular T regulatory cell is correlated with disease activity in systemic lupus erythematosus.
Follicular T regulatory (Tfr) cells inhibit follicular T helper (Tfh) cells mediated B cell responses. Tfh cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of Tfr cells in SLE remains unclear. The frequency of circulating Tfr and Tfh cells were examined in SLE patients and healthy controls. The frequency of circulating Tfr cell decreased and Tfh/Tfr ratio increased in SLE patients. Serum anti-dsDNA antibody level positively correlated with frequency of Tfh cells and Tfh/Tfr ratios but negatively correlated with the frequency of Tfr cells. Moreover, the frequency of Tfr and Tfh/Tfr ratio but not that of Tfh was correlated with diseases activity. In addition, increase in Tfr cell numbers and decrease in the Tfh/Tfr ratios were observed with successful treatments. Thus, Tfr cells should be considered as a biomarker for SLE and their role in the pathogenesis of SLE warrants further investigation.


FOXG1-Related Disorders: From Clinical Description to Molecular Genetics.
Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Mutations in loci other than MECP2 have also been found in individuals that have been labeled as atypical RTT. Among them, a mutation in the gene forkhead box G1 (FOXG1) has been involved in the molecular aetiology of the congenital variant of RTT. The FOXG1 gene encodes a winged-helix transcriptional repressor essential for the development of the ventral telencephalon in embryonic forebrain. Later, FOXG1 continues to be expressed in neurogenetic zones of the postnatal brain. Although RTT affects quasi-exclusively girls, FOXG1 mutations have also been identified in male patients. As far as we know, about 12 point mutations and 13 cases with FOXG1 molecular abnormalities (including translocation, duplication and large deletion on the chromosome 14q12) have been described in the literature. Affected individuals with FOXG1 mutations have shown dysmorphic features and Rett-like clinical course, including normal perinatal period, postnatal microcephaly, seizures and severe mental retardation. Interestingly, the existing animal models of FOXG1 deficiency showed similar phenotype, suggesting that animal models may be a fascinating model to understand this human disease. Here, we describe the impacts of FOXG1 mutations and their associated phenotypes in human and mouse models.


Expression pattern of leptin and leptin receptor (OB-R) in human gastric cancer.
To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia. By immunohistochemical staining using specific antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features. Both normal gastric epithelium and carcinoma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-R-positive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a significant correlation with the level of leptin expression. The expression levels of both leptin and OB-R tended to increase as the depth of tumor invasion or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic invasion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) patients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis. Overexpression of leptin and expression of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer.


Novel hard-block polyurethanes with high strength and transparency for biomedical applications.
Novel hard-block-only polyurethanes are prepared from 1,4-butanediol (BDO) and a pre-polymer synthesized separately from 1,3-bis (4-hydroxybutyl) tetramethyl disiloxane (BHTD) and 4,4'-diphenylmethane diisocyanate (MDI). Three (co)polymers using different proportions of these chain extenders were synthesized using reaction injection moulding, and their microstructure, mechanical properties and in vitro oxidative biostability were evaluated. These materials were found to form a single-phase system, and exhibit optical transparency, high elastic modulus and tensile strength, as well as significant in vitro oxidative biostability. By controlling the BDO/BHTD composition, the ductility can be tuned over orders of magnitude. These polyurethanes may be potentially suitable for biomedical applications, like electronic headers for defibrillators, pacemakers and neurostimulators, and orthopedic nail encapsulation.


Development and assessment of a new radioactive decay database used for dosimetry calculation.
The present paper discusses the technical issues and a scheme for their resolution before undertaking the development of a new radioactive decay database to succeed ICRP38. The scheme consists of the following procedures. (1) The consistency of nuclear structure data files used as input to the computer code EDISTR is established by referring to the latest nuclear parameters and by comparing the computed energies of emitted radiations with total decay energy. (2) A method for calculating detailed spectra of X rays and Auger electrons is incorported into EDISTR to enhance the treatment of atomic relaxation processes initiated by electron vacancies from internal conversion and electron capture. (3) Quality assurance of the compiled data is undertaken by comparisons with experimental data and other decay databases prepared from different computer codes and libraries. JAERI and ORNL are cooperating to implement the scheme in order to assemble a comprehensive radioactive decay database including over 1000 nuclides.


Construction of an efficient artificial light-harvesting system based on hyperbranched polyethyleneimine and improvement of photocatalytic performance.
An artificial light-harvesting system (ALHS) was developed in aqueous solution by employing the electrostatic co-assembly of a tetraphenylethylene derivative modified with two sulfonate groups (TPE-BSBO) and hyperbranched polyethyleneimine (PEI) as the energy donors, and 4,7-bis(2-thienyl)-2,1,3-benzothiadiazole (DBT) as the energy acceptors. The ALHS exhibits not only high efficiency in energy transfer and conversion but also a significant enhancement in the generation of reactive oxygen species (ROS), especially superoxide anion radicals (O2˙-), facilitating its utilization in photocatalytic oxidation reactions.


Use of Probiotics for the Management of Acute Gastroenteritis in Children: An Update.
Since the publication of the 2014 European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Working Group (WG) on Probiotics and Prebiotics guidelines for the management of acute gastroenteritis (AGE), new evidence concerning the efficacy of probiotics has become available. This document provides updated recommendations on the use of probiotics for the treatment of AGE in previously presumed healthy infants and children. A systematic literature search was performed. All pooled analyses were explicitly performed for the current report. The WG graded the recommendations and assessed the certainty of the supporting evidence using the Grading of Recommendations, Assessment Development, and Evaluations tool. The recommendations were formulated if at least 2 randomized controlled trials that used a given probiotic were available. Despite the large number of identified trials, the WG could not identify 2 randomized controlled trial of high quality for any strain that provided benefit when used for treating AGE. The WG made weak recommendations for (in descending order in terms of the number of trials evaluating any given strain): Saccharomyces boulardii (low to very low certainty of evidence); Lactobacillus rhamnosus GG (very low certainty of evidence); L reuteri DSM 17938 (low to very low certainty of evidence); and L rhamnosus 19070-2 and L reuteri DSM 12246 (very low certainty of evidence). The WG made a strong recommendation against L helveticus R0052 and L rhamnosus R0011 (moderate certainty of evidence) and a weak recommendation against Bacillus clausii strains O/C, SIN, N/R, and T (very low certainty of evidence).


[Anticarcinogenic action of dietary supplement pheocarpin and its active component].
Anticarcinogenic action of dietary supplement Pheocarpin and its active component Natural Coniferous Complex (NCC), in particular, has been studied. Pheocarpin and NCC efficiently inhibited tumorigenesis in the mammary gland, large bowel, skin, cervix uteri and lungs. Pheocarpin offers considerable advantage as a means of reducing the risk of malignant disease.


[Pressure-flow relationships interpretation in idiopathic pulmonary arterial hypertension].
We analyze exercise-derived mean pulmonary artery pressure/cardiac index relationship to expand the concepts regarding its nature and to better identify "responders" in idiopathic pulmonary arterial hypertension patients. Mean pulmonary artery pressure/cardiac index relationship and extrapolated pressure to zero flow were obtained in 40 patients' breathing room air, oxygen 99.5% and hydralazine. The hemodynamic characteristics were analyzed for the cohort and separate for responders (n = 20) and non responders (n = 20) according to the acute response to vasodilator. We tested this previous criteria versus the Task Force on diagnosis and treatment prescribed by the European Society of Cardiology. The mean pulmonary arterial pressure-flow diagram of the total cohort (p < 0.01). No alterations in gas exchange or lung mechanics. For patients responders versus non-responders, the slope was abnormal 2.2(95%CI: 1.1-3.3) vs 5.89 (95% CI: 4.69 - 7.11), mmHg/L min/m2 and increased extrapolated pressure to zero flow (38.2 + 7.5 to 66.3 + 7.5 mmHg, p < 0.01). Without difference with oxygen 99.5%. With vasodilator effect, mean pulmonary arterial pressure decreased (52.1+9.5 a 40 + 5.5 mm Hg, p< 0.01) versus it did not change (96.2 + 8.5 vs 90 + 7.5 mmHg, p = 0.3), slope 1.15 (95% CI: 0.68 - 1.62) vs. 1.28 (95% CI: 0.78-1.78) mmHg/L min/m2, the extrapolated pressure to zero flow did not change (69.4 + 7.8 a 85.1 + 8.5 mmHg), p < 0.01 compared to control. In non-responders with vasodilator, mean pulmonary arterial pressure/cardiac index (90 + 7.5 mmHg, pendiente: 1.28, 95%IC: 0.78 - 1.78 mmHg/L min/m2) was different between responders <or> 40 mm Hg mean pulmonary arterial pressure. Pressure were 34 + 3 vs 45 + 4 mm Hg and slopes 1.14 (95%IC: 0.67 - 1.61 vs 2.22 (95%IC: 1.35 - 3.09 mm Hg/L min/m2) p < 0.01 respectively. Abnormalities of the mean pulmonary arterial pressure/cardiac index relationship exercise-derived seems to reflect "mainly arteriolar" increased lineal pulmonary vascular resistance in idiopathic pulmonary arterial hypertension patients. Both acute vasodilator response criteria are useful to identify responders and not responders in this patient population.


Rapid development of synaptic connections and plasticity between sensory neurons and motor neurons of Aplysia in cell culture: implications for learning and regulation of synaptic strength.
We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron-motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.


Salinicoccus halodurans sp. nov., a moderate halophile from saline soil in China.
A moderately halophilic, Gram-positive coccus, designated strain W24(T), was isolated from saline soil in Qinghai province, China. The isolate was able to grow at salinities of 0-24 % (w/v) NaCl (optimally at 8 %, w/v), at pH 5.5-9.0 (optimally at pH 7.5) and at 8-43 degrees C (optimally at 28 degrees C). The genomic DNA G+C content of strain W24(T) was 45.8 mol%. The predominant isoprenoid quinone was MK-6 and the cell wall contained lysine and glycine as diagnostic diamino acids. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. The major cellular fatty acids were iso-C(15 : 0), anteiso-C(15 : 0) and C(16 : 0). Based on 16S rRNA gene sequence analysis, strain W24(T) was found to be a member of the genus Salinicoccus and was related most closely to Salinicoccus hispanicus DSM 5352(T) (96.5 % sequence similarity). Based on data from the current polyphasic study, strain W24(T) is considered to represent a novel species of the genus Salinicoccus, for which the name Salinicoccus halodurans sp. nov. is proposed. The type strain is W24(T) (=CGMCC 1.6501(T)=DSM 19336(T)).


Hispolon-Loaded Liquid Crystalline Nanoparticles: Development, Stability, In Vitro Delivery Profile, and Assessment of Hepatoprotective Activity in Hepatocellular Carcinoma.
The present work describes the development and characterization of liquid crystalline nanoparticles of hispolon (HP-LCNPs) for treating hepatocellular carcinoma. HP-LCNPs were prepared by a top-down method utilizing GMO as the lipid and Pluronic F-127 as the polymeric stabilizer. The prepared formulations (HP1-HP8) were tested for long-term stability, where HP5 showed good stability with a particle size of 172.5 ± 0.3 nm, a polydispersity index (PDI) of 0.38 ± 0.31 nm, a zeta potential of -10.12 mV ± 0.05, an entrapment efficiency of 86.81 ± 2.5%, and a drug loading capacity of 12.51 ± 1.12%. Optical photomicrography and transmission electron microscopy images demonstrated a consistent, low degree of aggregation and a spherical shape of LCNPs. The effect of temperature and pH on the optimized formulation (HP5) indicated good stability at 45 °C and at pH between 2 and 5. In vitro gastrointestinal stability indicated no significant change in the particle size, PDI, and entrapment efficiency of the drug. The drug release study exhibited a biphasic pattern in simulated gastric fluid (pH 1.2) for 2 h and simulated intestinal fluid (pH 7.4) for up to 24 h, while the best fitting of the profile was observed with the Higuchi model, indicating the Fickian diffusion mechanism. The in vivo pharmacokinetic study demonstrated nearly 4.8-fold higher bioavailability from HP5 (AUC: 1774.3 ± 0.41 μg* h/mL) than from the HP suspension (AUC: 369.11 ± 0.11 μg* h/mL). The anticancer activity evaluation revealed a significant improvement in antioxidant parameters and serum hepatic biomarkers (SGOT, SGPT, ALP, total bilirubin, and GGT) in the diethyl nitrosamine-treated group of rats with the optimized LCNP formulation (HP5) vis-à-vis HP suspension.


A randomized trial of holmium laser vs thulium laser vs bipolar enucleation of large prostate glands.
To compare the outcome and morbidity of bipolar transurethral enucleation of the prostate (B-TUEP) and thulium laser enucleation of the prostate (ThuLEP) with those of holmium laser enucleation of the prostate (HoLEP) in the treatment of large symptomatic benign prostatic obstruction (BPO) through a non-inferiority randomized controlled trial (NCT03916536). A total of 155 patients were recruited from a single centre between February 2019 and August 2020. All had BPO, with a prostate volume ≥80 ml. Patients were randomly assigned to HoLEP, ThuLEP or B-TUEP using computer-generated random tables in a 1:1:1 ratio. Participants, investigators and surgeons were blinded to group assignment until the date of the operation. Thereafter, the patients were followed up at 1, 3, 6 and 12 months. The primary outcome was maximum urinary flow rate (Qmax ) at 6 months. Secondary outcomes included assessment of other functional urinary variables, peri-operative records, and adverse events. There were 138 and 120 patients available for analysis at 6 and 12 months. There was no significant difference in Qmax between the groups at 6 and 12 months (P = 0.4 and P = 0.7, respectively), and no significant difference regarding International Prostate Symptom Score (IPSS), quality of life (QoL) or postvoid residual urine volume (PVR). The median (interquartile range) prostate-specific antigen (PSA) reductions (ng/ml) were similar in the three groups at last follow-up point (4.7 [2.2-7.1]; 5.6 [2.3-9.5] and 5 [3.4-10] after HoLEP, ThuLEP and B-TUEP, respectively). Differences in enucleation time, enucleation efficiencies and auxiliary manoeuvres were statistically insignificant (P = 0.1, 0.8 and 0.07, respectively). At 1 year, patients with prostate volumes >120 ml showed significant IPSS improvement in favour of HoLEP and ThuLEP (P = 0.01). Low- and high-grade adverse effects were recorded in 31 and five cases, respectively, with no statistically significant difference between the groups. We conclude that ThuLEP and B-TUEP are as safe and effective as HoLEP for the treatment of large-sized BPO. Significant PSA reductions indicate that there was effective adenoma enucleation with all three approaches. The study provides objective evidence that endoscopic enucleation of the prostate is a technique rather than energy dependent procedure.


Oral Appliance Effectiveness and Patient Satisfaction with Obstructive Sleep Apnea Treatment in Adults.
BACKGROUND Indication of oral appliances for the treatment of an obstructive sleep apnea (OSA) includes both patients with primary snoring and mild OSA, as well as patients with moderate to severe OSA who refuse other treatment or in whom such treatment failed. The aim of this study was to verify the effectiveness of current OSA treatment by objective measurements, and to assess by means of a questionnaire patients' satisfaction with oral appliances manufactured in our laboratory. MATERIAL AND METHODS The study enrolled 58 adult patients (40 men, 18 women) with mean age of 50.5 years; most were overweight or had class I obesity; mean baseline apnea-hypopnea index (AHI) value prior to the beginning of treatment was 31.3, range 0.6-71. RESULTS Average AHI reduction in the entire group was 10.4; 31% of patients experienced AHI reduction by at least 50%. Significant AHI reduction was proven when using the appliance. Appliances affect the reduction of AHI and patients tolerate the appliances well. CONCLUSIONS Oral appliances complement positive-pressure treatment and do not interfere with it in any way. Craniometric parameters seem to be applicable as predictors of success or failure of appliance treatment.


Vasomotion of renal blood flow in essential hypertension. Oscillations in xenon transit.
To assess the frequency and magnitude of phasic renal blood flow changes in essential hypertension, we applied an analytical method based on the estimation of power spectral density to xenon transit through the kidney. Despite similar age and gender distribution of the patients and exclusion of those with accelerated hypertension, mean renal blood flow was significantly lower in 100 patients with essential hypertension (299 +/- 8 ml/100 g/min) than in the 144 normal subjects (335 +/- 6 ml/100 g/min; p less than 0.001). Normalized power, the index of oscillatory behavior, was more than twice normal in patients with essential hypertension (p less than 0.001), but there was no difference in the frequency or cycle length of the oscillation. Two maneuvers that induced renal vasoconstriction, the application of cuffs to the thighs which were then inflated to diastolic blood pressure and an emotional provocation, reduced renal blood flow much more in patients with essential hypertension (p less than 0.01) in association with a striking increase in normalized power (p less than 0.001). The oscillations, which reflected not the phasic blood pressure change but rather the phasic change in renal perfusion, provided additional evidence that renal vasoconstriction plays an active role in the pathogenesis of essential hypertension.


Cardiac involvement and prognosis in acute mucocutaneous lymph node syndrome.
Cardiac involvement and prognosis were studied in the acute febrile mucocutaneous lymph node syndrome which recently has been found among Japanese infants and younger children. The reason for its particular predilection for the main coronary arteries and the pathologic process are discussed in relation to the pathogenesis and nutrient of the main coronary arteries.


Object attachment: Humanness increases sentimental and instrumental values.
People who hoard form intense attachments to their possessions and save items for sentimental and instrumental reasons. Feeling socially excluded may encourage these individuals to anthropomorphize objects (i.e., perceive them as human-like) to fulfill unmet belonging needs, which may increase the sentimental and instrumental values of objects, and then lead to stronger object attachment. We randomly assigned 331 participants with excessive acquisition tendencies to be excluded, included, or overincluded in an online ball-tossing game before presenting them with five objects that had human characteristics. Participants then completed measures assessing anthropomorphism, sentimental and instrumental values, and object attachment. Inconsistent with this study hypothesis, socially excluded participants did not rate unowned objects as more human-like than the included or overincluded participants; however, stronger anthropomorphism predicted greater instrumental and sentimental values, which then predicted greater object attachment. Sentimental and instrumental values may explain how stronger anthropomorphism may lead to greater object attachment. Learning that leads to anthropomorphism may help us better understand object attachment.


Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice.
Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes. 25-Hydroxycholesterol (25-OHC) is produced in cells from cholesterol by the enzyme cholesterol 25-hydroxylase (Ch25h) and is involved in lipid metabolism, inflammatory processes, and cell proliferation. Here, we investigated the role of hepatic Ch25h in the transition from metabolically healthy obesity to insulin resistance and diabetes. Using several different experimental approaches, we demonstrated the significance of Ch25h on the border of "healthy" and "diseased" states of obesity. Adenovirus-mediated Ch25h overexpression in mice improved glucose tolerance and insulin sensitivity and lowered HOMA-IR. Our data suggest that low hepatic Ch25h levels could be considered a risk marker for unhealthy obesity.


Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders.
Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.


[Single-row wire suture of the sigmoid in Goodwin operations].
In Goodwin operations the authors have closed the intestinal wound resulting from longitudinal sigmoidotomy using a single-row uninterrupted transverse suture with atraumatic monofile steel wire. This suture technique has proved to be safe. No complications which might be associated with it have been observed.


Prioritizing conservation efforts based on future habitat availability and accessibility under climate change.
The potential for species to shift their ranges to avoid extinction is contingent on both the future availability and accessibility of habitats with analogous climates. However, many previous studies used a single method that considered individual factors, while a few combined two factors to develop conservation strategies. Most studies that do so focus on identifying climate refugia or climate connectivity areas in fixed areas, ignoring the dynamic range shifting process of animals. Here, we combined habitat suitability and climate velocity with network analysis to quantify future habitat availability and accessibility under climate change, thereby assessing range shift potential and identifying conservation priority areas for migratory birds across the Yangtze River basin (YRB) in the 2050s under 4 climatic scenarios. Our results suggested that medium (i.e., 5-10 km/yr) and high (i.e., above 10 km/yr) climate velocity would threaten 18.65% and 8.37% of stable suitability areas. Despite low (i.e., 0-5 km/yr) climate velocity exposure, 50.15% of climate velocity-identified destinations had poorer habitat suitability than their sources. Integrating climate velocity and habitat suitability, a few but critica sites and paths were identified as priority protected areas, mainly in Sichuan and the mid-lower reaches of the YRB. Finally, we constructed a climate-informed protected priority areas network for migratory birds. Overall, we demonstrate the differences between habitat suitability and climate velocity in capturing biological responses to climate change. More importantly, we accounted for the dynamic process of species range shifts implied by climate velocity and future habitat suitability, which we then used to identify conservation priority areas. Therefore, this study can provide a novel insight into forecasting climate-driven distribution shifts and informing conservation priorities. This article is protected by copyright. All rights reserved.


Quality of life independently predicts long-term mortality but not vascular events: the Northern Manhattan Study.
Cardiovascular disease is a major contributor to morbidity and mortality, and prevention relies on accurate identification of those at risk. Studies of the association between quality of life (QOL) and mortality and vascular events incompletely accounted for depression, cognitive status, social support, and functional status, all of which have an impact on vascular outcomes. We hypothesized that baseline QOL is independently associated with long-term mortality in a large, multi-ethnic urban cohort. In the prospective, population-based Northern Manhattan Study, Spitzer QOL index (SQI, range 0-10, with ten signifying the highest QOL) was assessed at baseline. Participants were followed over a median 11 years for stroke, myocardial infarction (MI), and vascular and non-vascular death. Multivariable Cox proportional hazards regression estimated hazard ratio and 95% confidence interval (HR, 95% CI) for each outcome, with SQI as the main predictor, dichotomized at 10, adjusting for baseline demographics, vascular risk factors, history of cancer, social support, cognitive status, depression, and functional status. Among 3298 participants, mean age was 69.7 + 10.3 years; 1795 (54.5%) had SQI of 10. In fully adjusted models, SQI of 10 (compared to SQI <10) was associated with reduced risk of all-cause mortality (HR 0.80, 95% CI 0.72-0.90), vascular death (0.81, 0.69-0.97), non-vascular death (0.78, 0.67-0.91), and stroke or MI or death (0.82, 0.74-0.91). In fully adjusted competing risk models, there was no association with stroke (0.93, 0.74-1.17), MI (0.98, 0.75-1.28), and stroke or MI (1.03, 0.86-1.24). Results were consistent when SQI was analyzed continuously. In this large population-based cohort, highest QOL was inversely associated with long-term mortality, vascular and non-vascular, independently of baseline primary vascular risk factors, social support, cognition, depression, and functional status. QOL was not associated with non-fatal vascular events.


Pelvic fracture after scoliosis surgery in osteogenesis imperfecta: a case report.
Literature, describing scoliosis in patients of osteogenesis imperfecta (OI), favors operative treatment as soon as possible in the form of fixation with instrumentation and fusion to prevent curve progress and pulmonary function deterioration. There are various complications associated with the treatment of scoliosis in OI before, during, and after surgery because of poor bone quality in such patients. We presented a case report of stress-induced transverse fracture of both iliac wings after scoliosis surgery in a 16-year-old girl with OI, who was treated conservatively. Owing to unusual symptoms and continuous dull pain in her back, the diagnosis was delayed during which the conditions made her life miserable. This report also suggests that a stress fracture should be on high suspicion in OI patients when they present with minor difference in the nature of pain.


Roles of arachidonate metabolites in thrombus formation and leukocyte migration: analyses at microcirculatory level.
Thromboxane (TX) A2 is involved in platelet aggregation, which initiates thrombus formation. The platelet thrombi in microcirculation, however, are not homogeneous in nature. Two types of platelet thrombi, formed in an arteriole of the hamster cheek pouch, could be differentiated in sensitivity to indomethacin and PGI2. The "stable thrombus" was sensitive to indomethacin, and was not inhibited by PGI2, when applied after the formation, whereas the "ADP-induced thrombus" was sensitive to PGI2, but insensitive to indomethacin. These characteristics were reflected by two types of aggregation of composed platelets. Leukotriene B4 induced adhesion of the leukocytes on the venular wall in very low concentrations, when perfused over the microvasculature of hamster cheek pouch. The leukocyte adhesion on the venular wall was followed by migration into interstitial space. This adhesion was attributed to a change of leukocytes, rather than of the endothelial cell surface, as ascertained by selective microinjection of LTB4 with a glass capillary. LTB4 was also accumulated in the ischemic cardiac tissue after ligation of the rat coronary artery, followed by a peak in the accumulation of leukocytes. Inhibition of the LTB4 generation by a 5-lipoxygenase inhibitor not only suppressed the leukocyte count by 40%, but also the infarct size by 34.4%.


The Effect of LVAD Pressure Sensitivity on the Assisted Circulation Under Consideration of a Mitral Insufficiency: An In Vitro Study.
Current left ventricular assist devices (LVADs) differ with respect to their pump characteristics as described by the pump characteristic curve (also called HQ-curve). Pressure sensitive LVADs depict a flat characteristic curve while most available LVADs have a steep, less pressure sensitive characteristic curve. This in vitro study investigated the effect of LVAD pressure sensitivity with a focus on the afterload of the right ventricle (RV) which is one out of many factors influencing right heart failure (RHF). To this end, two laboratory pumps differing in pressure sensitivity were tested as LVAD in an established, active mock circulation loop (MCL). The MCL represented patients with left heart failure and mitral insufficiency as another contributing factor to RV afterload. The results show that the pressure-volume loop (PV-loop) of the left ventricle (LV) undergoes a leftward and thus somewhat of a downward-shift for highly pressure sensitive support. Consequently, the LV is unloaded to a higher degree at comparable arterial blood pressure and identical cardiac output, pulmonary and systemic vascular resistance and ventricular contractility. This causes a concomitant decrease of RV afterload. This effect seems to be due to increased unloading during systole. In case of a severe concomitant mitral insufficiency and looking at left atrial pressure, the difference is 18.5%. Without mitral insufficiency, the difference is reduced to 10.2%.


Development of small cyclic peptides targeting the CK2α/β interface.
In this work, an iterative cycle of enzymatic assays, X-ray crystallography, molecular modelling and cellular assays were used to develop a functionalisable chemical probe for the CK2α/β PPI. The lead peptide, P8C9, successfully binds to CK2α at the PPI site, is easily synthesisable and functionalisable, highly stable in serum and small enough to accommodate further optimisation.