Interferon activity is not detected in blastocyst secretions and does not induce decidualization in mice.
Mouse trophoblast cells synthesized and secreted proteins during the peri-implantation period, some in the molecular size range of alpha interferons (IFN-alpha), known mediators of the maternal recognition of pregnancy in sheep and cows. However, conditioned media samples containing secreted proteins from Day-5 mouse blastocysts or from trophoblast outgrowths did not contain detectable levels of antiviral activity indicative of IFN. In addition, it was not possible to induce a decidual reaction in suitably sensitized uteri with intraluminal instillation of IFN-alpha. The results indicate that IFNs are probably not involved in the maternal recognition of pregnancy at the time of implantation in the mouse.


Laparotomy in mice induces blood cell expression of inflammatory and stress genes.
Surgical trauma induces immune and stress responses although its effects on postsurgical inflammatory and stress gene expression remain poorly characterized. This study sought to improve current scientific knowledge by investigating the effects of laparotomy on mouse blood cell inflammatory and stress gene expression. Three-month-old male C57BL/6J mice were subjected to 2% isoflurane or 2% isoflurane with laparotomy and sacrificed 4 h postintervention. Blood was collected and blood cell expression of 158 genes central to inflammatory and stress responses was assayed using quantitative polymerase chain reaction arrays. Mice subjected to isoflurane with laparotomy, compared with mice receiving isoflurane alone, had >2-fold upregulation of genes in inflammation (Osm, IL1rn, IL1b, and Csf1), oxidative stress (Hmox1), heat shock (Hspa1b), growth arrest (Cdkn1a), and DNA repair (Ugt1a2). These genes demonstrated similar expression patterns by Pearson correlation and cluster analysis. Thus, laparotomy induces coordinated, postsurgical blood cell expression of unique inflammatory and stress genes whose roles in influencing surgical outcomes need further investigation.


[Traumatic foreign body embolism from the basilic vein].
Foreign body embolisms can be traumatic and iatrogenic. Traumatic foreign body emulsion are almost always induced by gunshot wounds. Central vessels with a large lumen are the most frequent site of entry. Foreign bodies are transported to peripheral body areas or produce pulmonary embolism. Clinical manifestations are dependent on the size and place of the foreign body. In this report a case of traumatic foreign body embolism is presented, in which the basilic vein was the site of entrance and the foreign body was transported to the right lower lobe of the lung. Foreign body embolism should always be considered in the differential diagnosis in the case of patients with no visible foreign body in the injury. Treatment is dependent on the clinical signs and on size and shape of the foreign body. Symptomatic foreign body embolism and large irregularly shaped foreign bodies should be extracted. When only a small foreign body with no clinical symptoms is present conservative management is most appropriate.


Epidoxoform: a hydrolytically more stable anthracycline-formaldehyde conjugate toxic to resistant tumor cells.
The recent discovery that the formaldehyde conjugates of doxorubicin and daunorubicin, Doxoform and Daunoform, are cytotoxic to resistant human breast cancer cells prompted the search for hydrolytically more stable anthracycline-formaldehyde conjugates. Doxoform and Daunoform consist of two molecules of the parent drug bound together with three methylene groups, two forming oxazolidine rings and one binding the oxazolidines together at their 3'-amino nitrogens. The 4'-epimer of doxorubicin, epidoxorubicin, reacts with formaldehyde at its amino alcohol functionality to produce a conjugate, Epidoxoform, in 59% yield whose structure consists of two molecules of epidoxorubicin bound together with three methylene groups in a 1, 6-diaza-4,9-dioxabicyclo[4.4.1]undecane ring system. The structure was established from spectroscopic data and is consistent with products from reaction of simpler vicinal trans-amino alcohols with formaldehyde. Epidoxoform hydrolyzes at pH 7.3 to an equilibrium mixture with dimeric and monomeric epidoxorubicin-formaldehyde conjugates without release of formaldehyde or epidoxorubicin. The hydrolysis follows the rate law (A if B) if C + D where A (Epidoxoform) is in rapid equilibrium with B, and B is in slow equilibrium with C and D. The forward rate constant for A/B going to C+D gives a half-life of approximately 2 h at 37 degrees C. At equilibrium the mixture is stable for at least 2 days. At pH 6.0, hydrolysis proceeds with first-order kinetics to epidoxorubicin and formaldehyde with a half-life of 15 min at 37 degrees C. Epidoxoform and epidoxorubicin plus formaldehyde react with the self-complementary DNA octamer (GC)4 to yield five drug-DNA adducts which have structures analogous to the doxorubicin-DNA adducts from reaction of Doxoform with (GC)4. Epidoxoform is 3-fold more toxic to MCF-7 human breast cancer cells and greater than 120-fold more toxic to MCF-7/ADR resistant cells than epidoxorubicin. Epidoxoform in equilibrium with its hydrolysis products is greater than 25-fold more toxic to resistant cells with respect to epidoxorubicin.


Intravitreal clindamycin for toxoplasmic retinochoroiditis.
To report outcomes of off-label use of intravitreal clindamycin in the treatment of toxoplasmic retinochoroiditis. In a noncomparative, retrospective, interventional case series, we reviewed the charts of six consecutive patients with toxoplasmic retinochoroiditis who were treated with intravitreal injection of clindamycin (1.0 mg/0.1 mL) because of intolerance to or disease progression despite oral microbial treatment. The primary outcome measures were change in Snellen visual acuity, resolution of inflammation, and adverse events. Injection of intravitreal clindamycin was associated with control of toxoplasmic retinochoroiditis and resolution of vitreous inflammation in all six patients. Five patients had improvement in visual acuity. One patient's vision was limited because of macular scarring. Four patients underwent concomitant pars plana vitrectomy (PPV) at the time of injection. One patient who had concomitant clindamycin injection and PPV developed a retinal detachment postoperatively. Intravitreal clindamycin injection, alone or in conjunction with PPV, was associated with resolution of toxoplasmic retinochoroiditis in six patients.


The ecology of white-handed and pileated gibbons in a zone of overlap and hybridization in Thailand.
The study of related species in contact zones can elucidate what factors mediate species coexistence and geographical distributions. We investigated niche overlap and group interactions of two gibbon species and their hybrids co-occurring in a zone of overlap and hybridization. The location, composition and behavior of white-handed, pileated, and mixed-species gibbon groups were studied by following them during 31 consecutive months in a relatively large part of the contact zone. Twenty groups of white-handed gibbon were mapped followed by nine groups of pileated gibbons and five mixed-species groups. White-handed, pileated and mixed-species groups had similar sizes and composition, ate a high proportion of fruits, shared a large number of species in their diets, and presented similar habitat preferences. Group home range sizes did not differ between species and overlapped little with neighboring groups irrespective of species, and intraspecific and interspecific encounter rates were similar. Ecological similarities support that competition between the gibbon species exists and takes the form of interspecific territoriality. However, we could not find any clear mechanism of niche partitioning favoring coexistence between species. Our findings suggest that the contact zone is unstable and is maintained by dispersal inward from groups of the parental species. The relatively low numbers of mixed-species groups and hybrids found suggests a high degree of premating reproductive isolation, perhaps mediated by interspecific miscommunication. The existence of hybrids and backcrosses potentially undetectable from phenotypic characters alone raises the possibility of more widespread introgression than has been evident. Hence, while interspecific territoriality should reduce the rate of gene transfer, it would not necessarily present a barrier to introgression into contiguous populations of the opposite species.


Connections of the small bipolar cells with the photoreceptors in the turtle. An electron microscope study of Golgi-impregnated, gold-toned retinas.
The connections between photoreceptors and the small bipolar cells with a Landolt club in the turtle retina (Pseudemys scripta elegans) were analyzed with the electron microscope after Golgi impregnation and gold toning. The dendritic tree of several bipolars was partially or completely reconstructed from continuous series of thin sections. All bipolar cells studied established both basal and invaginating junctions with cone pedicles; in invaginating junctions, their dendrites invariably ended as the central process of triads. Dendrites of this bipolar cell type make invaginating synapses, basal junctions, or a mixture of both. In turn, each pedicle found within the dendritic field of the bipolar cell contacts it with a mixture of invaginating and basal junctions; furthermore, each pedicle synapses with more than one dendrite from the same bipolar cell. All small bipolar cells examined also synapse with rod pedicles; the geometry of the connections and the types of synapses are the same for both rods and cones. The fact that small turtle bipolars can form both basal and invaginating contacts with a single cone indicates that the polarity of the postsynaptic response can not be predicted on the basis of the structure of the photoreceptor-to-bipolar cell synapse.


Determination of multicanonical weight based on a stochastic model of sampling dynamics.
Based on the stochastic interpretation of the sampling process modeled by a Langevin equation, we present an effective iteration scheme to determine the weight in multicanonical molecular dynamics. Our method enables an automatic determination of the weight producing a uniform energy sampling via an iterative cancellation of the deterministic force in a Langevin equation. The deterministic force has been calculated from the energy trajectory by identifying the moments of the transition probability of a Fokker-Planck equation associated with a Langevin equation. The intimate relationship between the sampling process and the stochastic dynamics has been verified by applying the iteration scheme to a helix-coil transition of the 8-polyalanine system in a gas phase.


Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception.
MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception.


Chronic phalaris toxicity in eastern grey kangaroos (Macropus giganteus).
Seven eastern grey kangaroos (Macropus giganteus) grazing pastures including Phalaris spp. in Victoria showed neurological deficits characterised by ataxia, head tremors and collapse. Gross examination of the brains and spinal cords of affected kangaroos showed a greenish discolouration in several regions of the grey matter. Histologically, intracytoplasmic accumulation of pigment granules was detected in the neurons, most prominently in the thalamus, brainstem and ventral horns of the spinal cord. Pigment granules were positive to stains used for identification of melanin, including Fontana-Masson stain and Schmorl's reaction. The combination of clinical signs and obvious neuronal pigmentation is consistent with chronic Phalaris spp. toxicity, a condition well documented in domestic ruminants.


The influence of aldosterone on the development of left ventricular geometry and hypertrophy in patients with essential hypertension.
The identification of risk factors for the initiation of left ventricle hypertrophy (LVH), which is an independent risk factor for cardiovascular mortality and morbidity in hypertensive patients, is very important. The objective of the present study was to identify the relationship of aldosterone with LVH and different geometrical patterns of left ventricle that develop in patients with essential hypertension. A total of 83 patients with essential hypertension (44 females, mean age, 51 +/- 8 years, 39 males, mean age, 57 +/- 10 years) were included in this study. Thirty-two had LVH. When evaluated according to the geometrical patterns of LVH, 18 patients had concentric LVH, 14 had eccentric LVH, and 17 had concentric remodeling. Thirty-four patients had normal left ventricle geometry. Two weeks after the cessation of antihypertensive medications, sodium, potassium, and proteinuria in 24-hour urine samples and plasma aldosterone levels and plasma renin activity were measured. Plasma aldosterone levels of the patients with LVH were found to be significantly higher (9.92 +/- 6.34 ng/dL versus 5.83 +/- 3.5 ng/dL, P < 0.01). The difference between plasma renin activities was not statistically significant. Linear regression analysis revealed that plasma aldosterone level and age were independent parameters increasing left ventricle mass index. The plasma aldosterone levels of patients with concentric hypertrophy of the left ventricle were significantly higher than those of patients with normal geometry and concentric remodeling. There was no significant difference between plasma renin activities. Twenty-four hour urine protein concentrations of the patients with LVH were found to be significantly higher and sodium to be significantly lower. Plasma aldosterone levels seem to be correlated with LVH especially with concentric hypertrophy of the left ventricle in patients with essential hypertension.


An Open-Framework Structured Material: [Ni(en)2]3[Fe(CN)6]2 as a Cathode Material for Aqueous Sodium- and Potassium-Ion Batteries.
Open-framework structured materials such as Prussian blue analogues and sodium superionic conductor (NASICON) materials have been regarded as promising electrode candidates for aqueous batteries. These materials exhibit outstanding long cycle stability and high rate capacity retention, due to their high ion diffusive rate in the crystal and the stable structure maintenance in the electrochemical reaction process. Herein, an open-framework structured material [Ni(en)2]3[Fe(CN)6]2 (NienHCF) is prepared and first used as a cathode material for aqueous sodium- and potassium-ion batteries. The resultant material exhibits a high output potential and outstanding cycle performance (93.4% after 500 cycles at 1 A g-1) in K-ion batteries. Meanwhile, the electrochemical reaction mechanism is investigated. After coupling with the activated carbon anode, the K-ion full cell has 91.5% capacity retention at 5 A g-1 and retains 77.2% after 1000 cycles at 0.5 A g-1, exhibiting the potential as an electrode material for rechargeable aqueous K-ion and Na-ion batteries.


The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: A meta-analysis.
This review and meta-analysis aimed to systematically evaluate the clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C (MMC) in patients with nonmuscular invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). The Embase, PubMed, CNKI, CBM, WANGFANG, VIP, Cochrane Library, and Clinicaltrial.com databases were searched for articles published before April 2022. The experimental group was treated with intravesical instillation of MMC assisted by equipment, including radiofrequency-induced thermochemotherapy, conductive thermochemical therapy, electromotive drug administration, or locoregional hyperthermia. The control group was treated with simple MMC perfusion. The outcomes of interest in the meta-analysis were recurrence, progression, side-effects, gross haematuria, and bladder irritation. A total of 15 studies that enrolled 1,190 patients were included in the meta-analysis. Compared to that of the control group, device-assisted intravesical instillation of MMC significantly reduced both tumour recurrence (odds ratio [OR] = 0.32, 95% confidence interval [CI] [0.24, 0.42], P <0.00001) and progression (OR = 0.29, 95% CI [0.12, 0.67], P = 0.004). There were no significant differences between the two groups in terms of safety (OR = 1.21, 95% CI [0.66,2.21], P = 0.54), bladder irritation (OR = 1.06, 95% CI [0.72,1.55], P = 0.78), or gross haematuria (OR = 1.11, 95% CI [0.64,1.94], P = 0.72). Equipment-assisted intravesical instillation of MMC significantly reduced the recurrence and progression of patients with NMIBC who underwent TURBT and improved their quality of life. Given the significant heterogeneity in research quality and sample size among earlier studies, more prospective, multicentre, large sample randomized controlled trials are needed to supplement and verify this in the future.


T cell antigen receptor dependent signalling in human lymphocytes: cholera toxin inhibits interleukin-2 receptor expression but not interleukin-2 synthesis by preventing activation of a protein kinase C isotype, PKC-alpha.
Activation and translocation of protein kinases C is a key event in the regulation of T lymphocyte activation, proliferation and function. Stimulation of human peripheral blood lymphocytes with the monoclonal antibody BMA 031 raised against the T cell antigen receptor led to a bimodal activation of protein kinases C. The immediate activation and translocation of the protein kinase C isoform PKC-alpha was followed by activation and translocation of the protein kinase C-beta isoenzyme after 90 min of stimulation. Pretreatment of the cells with cholera toxin for 90 min completely abolished activation of protein kinase C-alpha. In sharp contrast, activation and translocation of protein kinase C-beta was not influenced by the bacterial toxin, suggesting that activation and translocation of different protein kinase C isoenzymes are regulated by distinct mechanisms of transmembrane signalling coupled to the T cell antigen receptor/CD3 complex. The expression of high affinity IL-2 receptors was completely inhibited by cholera toxin, while IL-2 synthesis and secretion were not influenced in BMA 031-stimulated human lymphocytes. Extensive control experiments have shown that the effects of cholera toxin were not mediated by its B subunit, and were independent of elevation of intracellular cAMP concentration, suggesting that cholera toxin interfered with a signalling pathway leading to activation of protein kinase C-alpha, which could be responsible for the inhibition of IL-2 receptor expression. This hypothesis was substantiated by the finding that upon introduction of antibodies against protein kinase C-alpha, IL-2 receptor gene expression was completely suppressed. The results suggest, that protein kinase C-alpha might be the major protein kinase C isoenzyme of a signal transduction cascade regulating IL-2 receptor expression in stimulated human lymphocytes.


Sliding through a superlight granular medium.
We explore the penetration dynamics of an intruder in a granular medium composed of expanded polystyrene spherical particles. Three features distinguish our experiment from others studied so far in granular physics: (a) the impact is horizontal, decoupling the effects of gravity and the drag force; (b) the density of the intruder rho(i) is up to 350 times larger than the density of the granular medium rho(m); and (c) the way the intruder moves through the material, sliding at the bottom of the column with small friction. Under these conditions we find that the final penetration D scales with (rho(i)/rho(m)) and the drag force Fd and D saturate with the height of the granular bed.


Unusual hydrogen bonding behavior in binary complexes of coinage metal anions with water.
We have studied the interaction of atomic coinage metal anions with water molecules by infrared photodissociation spectroscopy of M-.H2O.Ar(n) clusters (M=Cu, Ag, Au; n=1, 2). We compare our observations with calculations on density-functional and coupled cluster levels of theory. The gold anion is bound to the water molecule by a single ionic hydrogen bond, similar to the halide-water complexes. In contrast, zero-point motion in the silver and copper complexes leads to a deviation from this motif.


Modeling the instantaneous dose rate dependence of radiation diode detectors.
The sensitivity S of Si diodes generally increases with an increase in the instantaneous dose rate r of the radiation beam from clinical linear accelerators. A theoretical model is established to understand the physical origin of this dependence. During a radiation exposure, a portion of the excess minority carriers (electrons or holes) generated in the diode is captured by the R-G (recombination-generation) centers and is recombined with the majority carriers. The captured portion depends on the excess minority-carrier concentration delta p (proportional to r), the R-G center concentration N(t), and the minority-carrier capture cross-sections (sigma(n) for electrons and sigma(p) for holes) by the R-G center. When r increases, the R-G center concentration may not be sufficient to keep the recombination portion constant, which leads to an increase in diode sensitivity because a larger fraction of the charge will be collected. Larger majority-carrier concentration increases the recombination probability of the excess minority carriers and thus decreases the r dependence. The ratio of minority-carrier capture cross-sections, sigma(p)/sigma(n), influences the magnitude of the r dependence and also differentiates the r dependence between n-type and p-type diodes. A number of different circumstances can occur in diodes. When sigma(p) > sigma(n), such as for the dominant R-G center generated by electron radiation, the sensitivity is more dependent on r in an n-type diode than in a p-type diode if all the other device parameters are the same. When sigma(p) < sigma(n), the sensitivity is then more dependent on r in a p-type diode than in an n-type diode. The condition of sigma(p) < sigma(n) can occur when R-G centers with this property are generated by the foundry die process. A diode could have very small r dependence due to large R-G center concentration, generated by heavy platinum doping or radiation accumulated dose. Experimental data are compared with theory.


Tutorials and workshops.
Provides an abstract for each of the tutorial presentations and a brief professional biography of each presenter. The complete presentations were not made available for publication as part of the conference proceedings.


Intracarotid slow bolus injection of nimodipine during angiography for treatment of cerebral vasospasm after SAH. A preliminary report.
Nimodipine was given as an intracarotid slow bolus injection in six patients with subarachnoid hemorrhage (SAH) due to rupture of a cerebral aneurysm, with angiographically demonstrated vasospasm. The patients were followed by serial angiograms for demonstration of the effect of nimodipine on vasospasm. After angiography, all patients were treated with a constant venous infusion of this new calcium antagonist. Although the therapeutic regimen was started only a few hours after onset of vasospasm, there was no change in cerebral vessel caliber detectable on angiograms following the intracarotid injection. Three patients died, two patients finally recovered with neurological deficits due to cerebral ischemia, and one patient with asymptomatic vasospasm remained symptom-free. Although nimodipine may act to prevent cerebral vasospasm after SAH, the authors believe that the intracarotid application is not effective after vasospasm has occurred.


[Efficacy of bioregulative drugs in the treatment of otitis media with effusion associated with rhinosinusitis and adenoiditis].
Improving of otitis media with effusion (OME) with rhinosinusitis (RS) and adenoiditis treatment effectiveness. The study included 112 patients 12-18 y.o. with otitis media with effusion, who were divided into 2 groups depending on the treatment scheme. The Group I (the main group) patients treatment included Traumeel S and Euphorbium compositum Nasentropfen S in addition to the standard treatment, and the Group II (comparison), children were prescribed standard therapy. Patients of both groups were divided into 3 subgroups depending on the upper respiratory tract inflammation symptoms: A - patients with adenoiditis; B - with rhinosinusitis and C - combination of adenoiditis and rhinosinusitis. The comparison group (groups IIB and IIC) treatment scheme (children with rhinosinusitis) included topical corticosteroids and the main group patients didn't receive corticosteroids. All patients went through complaints and anamnesis collection, routine otorhinolaryngological and instrumental examination before and after treatment. Analysis of treatment results demonstrated high efficacy of multicomponent drugs with low doses of active ingredients in the therapy of patients with OME, regardless of comorbid pathology. Significantly better results were obtained in the patients treated with bioregulatory drugs when comparing the outcomes of OME therapy in combination with adenoiditis (groups IA and IIA). Comparable efficacy results were obtained in the treatment group of patients with OME associated with RS (in groups IB and IIB as well as in groups IC and IIC), where GCS was received in the comparison group. The high efficacy and safety of bioregulatory drugs makes the use of these agents a promising treatment for patients with OME, RS and adenoiditis.


Efficiency of quantum vs. classical annealing in nonconvex learning problems.
Quantum annealers aim at solving nonconvex optimization problems by exploiting cooperative tunneling effects to escape local minima. The underlying idea consists of designing a classical energy function whose ground states are the sought optimal solutions of the original optimization problem and add a controllable quantum transverse field to generate tunneling processes. A key challenge is to identify classes of nonconvex optimization problems for which quantum annealing remains efficient while thermal annealing fails. We show that this happens for a wide class of problems which are central to machine learning. Their energy landscapes are dominated by local minima that cause exponential slowdown of classical thermal annealers while simulated quantum annealing converges efficiently to rare dense regions of optimal solutions.


Molecular changes in brain tumors: prognostic and therapeutic impact.
This review focuses on recent advances in the molecular biology of the main primary brain tumors (gliomas, medulloblastomas, and ependymomas), with particular emphasis on prognostic markers and potential therapeutic targets. Current biologic markers are useful for predicting prognosis (e.g. 1p/19q codeletion in grade 2 and 3 gliomas, nuclear beta-catenin expression in medulloblastoma) or response to the treatment (e.g. the methyl guanyl methyl transferase promoter methylation status). Recent gene profiling studies have identified specific molecular signatures that permit a molecular classification and that also provide new, potentially useful prognostic markers. The studies have also shown a striking parallel between central nervous system ontogenesis and the oncogenesis of brain tumors. By elucidating the underlying activated molecular pathways, these approaches provide the basis for a biologic therapy to target the critically activated pathways. Important advances have been made in the biologic understanding, molecular subclassification, and identification of prognostic markers in brain tumors, thereby improving the current classifications. Such data provide a rational basis for current and future targeted biologically based strategies.


Vancomycin resistant enterococcal (VRE) colonization among patients treated in intensive care units at the National Hospital of Sri Lanka, and determination of genotype/s responsible for resistance
The aim of this study was to assess the epidemiology of VRE colonization among patients in the intensive care units (ICU) of the National Hospital of Sri Lanka (NHSL). A cross sectional study was carried out on 218 patients admitted to 12 ICUs of the NHSL from January to March 2012. Rectal swabs were collected on day 0, 4, 8 and every 4th day thereafter till discharge. Enterococci were isolated on selective media and identified up to species level using standard bacteriological procedures. Standardized disc diffusion antibiotic susceptibility testing to ampicillin, teicoplanin and vancomycin was performed using the Clinical and Laboratory Standards Institute (CLSI) method. Minimum inhibitory concentrations to vancomycin were determined, using the E-test in strains showing intermediate or frank resistance to vancomycin by disc diffusion. Genotype determination (van A / van B) was carried out on isolates identified as VRE using the polymerase chain reaction. Patients positive for VRE colonization were followed up to discharge or death. VRE prevalence in the study sample was 5%. Univariate analysis showed that the use of metronidazole (odds ratio [OR] :15.73;95% 95% confidence interval [CI] : 3.94-62.67,P<0.05) or teicoplanin (OR: 12.56; 95% CI:2.65 – 59.52, p< 0.05) and diabetes (OR: 05.13; 95% CI: 1.36 – 18.7, p< 0.05) or hemodialysis during ICU stay (OR: 7.38 ;95% CI : 1.69-32.16, P<0.05) were associated with an increased risk of VRE colonization. The 5% prevalence of VRE colonization detected signals the emergence of VRE in the intensive care setting in Sri Lanka.


IRF6 and SPRY4 Signaling Interact in Periderm Development.
Rare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting. Similarly, variants within genes that encode receptor tyrosine kinase (RTK) signaling components, including members of the FGF pathway, EPHA3 and SPRY2, also contribute risk for isolated orofacial clefting. In the mouse, loss of Irf6 or perturbation of Fgf signaling leads to abnormal oral epithelial adhesions and cleft palate. Oral adhesions can result from a disruption of periderm formation. Here, we find that IRF6 and SPRY4 signaling interact in periderm function. We crossed Irf6 heterozygous ( Irf6+/-) mice with transgenic mice that express Spry4 in the basal epithelial layer ( TgKRT14::Spry4). While embryos with either of these mutations can have abnormal oral adhesions, using a new quantitative assay, we observed a nonadditive effect of abnormal oral epithelial adhesions in the most severely affected double mutant embryos ( Irf6+/-;TgKRT14::Spry4). At the molecular level, the sites of abnormal oral adhesions maintained periderm-like cells that express keratin 6, but we observed abnormal expression of GRHL3. Together, these data suggest that Irf6 and RTK signaling interact in regulating periderm differentiation and function, as well as provide a rationale to screen for epistatic interactions between variants in IRF6 and RTK signaling pathway genes in human orofacial clefting populations.


Use of a small particle solid-core packing for improved efficiency and rapid measurement of sirolimus and everolimus by LC-MS/MS.
Measurement of whole blood sirolimus and everolimus is required in order to optimize patient treatment following solid organ transplant. Assay by LC-MS/MS is increasingly preferred; however efficient use of the instrument and short turnaround times are crucial. Use of a 1.6 µm solid-core packing HPLC column (Cortecs) gave significant increases in efficiency, sensitivity and throughput compared with an existing method, following simple protein precipitation of small-volume (20 μL) whole blood samples. Sirolimus, everolimus and the stable isotopic internal standard ((13) C2 D4 - everolimus) eluted at around 0.8 min, and total analytical run time was 2.2 min, saving almost 4 min per sample compared with an existing method. Within-assay imprecision (CV) was 3.3-8.5%, and between-assay imprecision was 2.2-10.8%. Retrospective assay of external quality assurance samples and comparison of patient samples assayed in parallel showed only small differences (between +6.8 and -1.9%) in results using the Cortecs column when compared with the existing method. No significant interferences or ion suppression were observed. Copyright © 2015 John Wiley & Sons, Ltd.


New antigenic determinant common to human thymus leukaemia-associated antigens and common acute lymphoblastic leukaemia antigen.
In the present paper we demonstrate that there is an antigenic determinant common to two different types of human leukaemia-associated antigens, i.e. human thymus leukaemia-associated (HTL) antigens and common acute lymphoblastic leukaemia (cALL) antigen. In addition, there are distinct antigenic determinants which are unique to the HTL antigens or to the cALL antigen. The new, common antigenic determinant will be useful as a new differentiation marker of human haematopoietic cells as well as a new leukaemia-associated marker. In the present study, we used several different anti-human leukaemia antisera which include those prepared by immunizing rabbits (Nos. 7549 and 7550) with purified HTL antigens. The antisera 7549 and 7550, without any absorption, showed strong specificity as well as strong antibody activity toward leukaemia cells. These are the first anti-human leukaemia antisera, except for the monoclonal hybridoma antibodies, that show good specificity for leukaemia cells without prior absorption.


Comparative Trial of Continuous Flow Enteral and Intravenous Fluid Therapy in Horses.
Continuous flow enteral fluid therapy with isotonic and hypotonic enteral electrolyte solutions are as safe and effective as intravenous fluid therapy. The aim of this study was to carry out a comparative assessment between continuous flow enteral and intravenous (IV) fluid therapy in adult experimentally dehydrated horses. Six experimentally dehydrated adult mares were used in a study carried out in a 6 × 3 crossover design, which each animal received three different treatments (isotonic enteral fluid therapy-EsISO, hypotonic enteral fluid therapy-EsHYPO and intravenous fluid therapy with Lactate Ringer Solution-LR IV, all in continuous flow). Solutions were administered at a rate of 15 mL-1.kg-1.h-1 for 8 h, after 36 h of water and food deprivation. Serum and urinary biochemical assessment; urinary volume, pH and specific gravity; and blood gas analysis were measured at -36, 0, 2, 4, 6, and 8 h. The dehydration period (DP) caused discrete hydroelectrolytic and acid base imbalances. The EsISO, EsHYPO and LR IV increased blood volume. Enteral solutions restored the imbalances yielded by the DP and all treatments increased urine volume. Also, the EsHYPO and LR IV showed no effects in acid base balance, while EsISO showed slightly acidifying effect. The present study certifies the efficacy and safety of isotonic and hypotonic continuous flow enteral fluid therapy in comparison to IV fluid therapy in dehydrated horses.


Neuronal Cholesterol Accumulation Induced by Cyp46a1 Down-Regulation in Mouse Hippocampus Disrupts Brain Lipid Homeostasis.
Impairment in cholesterol metabolism is associated with many neurodegenerative disorders including Alzheimer's disease (AD). However, the lipid alterations underlying neurodegeneration and the connection between altered cholesterol levels and AD remains not fully understood. We recently showed that cholesterol accumulation in hippocampal neurons, induced by silencing Cyp46a1 gene expression, leads to neurodegeneration with a progressive neuronal loss associated with AD-like phenotype in wild-type mice. We used a targeted and non-targeted lipidomics approach by liquid chromatography coupled to high-resolution mass spectrometry to further characterize lipid modifications associated to neurodegeneration and cholesterol accumulation induced by CYP46A1 inhibition. Hippocampus lipidome of normal mice was profiled 4 weeks after cholesterol accumulation due to Cyp46a1 gene expression down-regulation at the onset of neurodegeneration. We showed that major membrane lipids, sphingolipids and specific enzymes involved in phosphatidylcholine and sphingolipid metabolism, were rapidly increased in the hippocampus of AAV-shCYP46A1 injected mice. This lipid accumulation was associated with alterations in the lysosomal cargoe, accumulation of phagolysosomes and impairment of endosome-lysosome trafficking. Altogether, we demonstrated that inhibition of cholesterol 24-hydroxylase, key enzyme of cholesterol metabolism leads to a complex dysregulation of lipid homeostasis. Our results contribute to dissect the potential role of lipids in severe neurodegenerative diseases like AD.


Anaerobiospirillum succiniciproducens bacteremia in a young child.
We report a case of Anaerobiospirillum succiniciproducens bacteremia in a young child who had no underlying disease. The case should alert microbiologists and physicians to an uncommon organism that is very often resistant to antibiotics normally prescribed empirically for infections caused by organisms of similar morphology and characteristics such as Campylobacter species.


[Organ changes induced by ergot derivative dopamine agonist drugs: time to change treatment guidelines in Parkinson's disease?].
Ergot derivative dopamine agonists, e.g. pergolide, bromocriptine, dihydroergocriptine used in treatment of Parkinson's disease can cause pleural, pericardial, retroperitoneal and valvular fibrotic changes. Case No 1: A 56-year-old woman with PD was treated with pergolide 3mg/24h since July 2002. In June 2003, edema of lower extremities was first noticed and echocardiography found a minor mitral regurgitation without any morphological changes of the valve. In January 2004, left- sided cardiac failure rapidly developed and echocardiography revealed multivalvular insufficiency with predominating severe mitral regurgitation. Mitral valve replacement was performed and pergolide was changed to ropinirole. Until now, neither cardiac functions nor motor status are sufficiently compensated. Case No 2: A 66-year-old-man with PD since 1996 was treated with pergolide 3 mg/day since 1999. In the beginning of 2004, leg edema appeared. On examination, bilateral hydronephrosis with ureteric strictures and incipient renal insufficiency was found. Bilateral ureteroplasty was performed and the histology showed periureteric fibrosis. Treatment with steroids was initiated and pergolide was changed to pramipexole. Despite the treatment, the fibrosis progressed, requiring ureteral stenting. Based on the literature review and on our own experience, we propose following guidelines to minimize the risk of complications: A. Not to use EAD as the first-line dopamine agonists. B. Regularly follow all patients treated with EAD, especially monitor the majorsymptoms: dyspnea, cough, fatigue, leg edema (also asymmetric), symptoms of urinary outflow obstruction, cardiac insufficiency, chest pain, heart murmur. An elevated ESR, C-reactive protein or anemia support the diagnosis. C. All symptomatic patients should undergo workup for serosal fibrosis (according to type of complication): chest X-ray or CT scan, spirometry, renal functions, renal ultrasound, CT of retroperitoneum. D. Before the introduction of EAD therapy, examine the renal functions, perform chest X-ray and echocardiography. Screening echocardiography should be performed in 3-6 months and subsequently in every 6-12 months.


Prevalence study on potential drug-drug interaction in cancer patients in Piacenza hospital's Onco-Haematology department.
Background Cancer patients can be a human model of potential drug interactions. Usually they receive a large number of different medications, including antineoplastic agents, drugs for comorbid illness and medication for supportive care, however information about these interactions are fragmented and poor. Objective We assessed a prospective study to evaluate the prevalence of drug interaction among patients hospitalized in the Onco-Haematology department, Hospital of Piacenza. Methods Data on drugs administered for cancer, comorbidities, or supportive care were collected from different computerized prescription software in use in the department; we compared them with a database to focus on the co-administration of drugs. A literature review was performed to identify major potential drug interaction and to classify them by level of severity and by strengths of scientific evidence. Results In this study 284 cancer patients were enrolled; patients had taken an average of seven drugs on each day of therapy plus chemotherapeutic agents, we identified 67 potential drug interactions. At least 53 patients had one potential drug interaction. Of all potential drug interactions 63 were classified as moderate severity and only four as major. In 55 cases chemotherapeutic agents were involved in possible interactions with supportive care drugs, meanwhile in 12 cases the potential drug interactions were between supportive care drugs. Conclusions In our centre, thanks to a computerized prescription software, integrated with caution alarm in case of possible interaction, we had a lower rate of potential drug interactions than the one from literature. It is possible to improve the software integrating the alarm with the potential drug interactions between chemotherapy agents and supportive care drugs.


A topological model for the general aromatic amino acid permease, AroP, of Escherichia coli.
The general aromatic amino acid permease, AroP, of Escherichia coli is responsible for the active transport of phenylalanine, tyrosine, and tryptophan. A proposed topological model for the AroP permease, consisting of 12 hydrophobic transmembrane spans connected by hydrophilic loops, is very similar to that of the closely related phenylalanine-specific permease. The validity of this model and its similarity to that of the PheP permease were investigated by studying fusion proteins of AroP permease and alkaline phosphatase. Based on the results obtained from the AroP-alkaline phosphatase sandwich fusions, we have significantly revised the proposed topological model for AroP in two regions. In this modified AroP topological model, the three charged residues E151, E153, and K160 are repositioned within the membrane in span 5. These three residues are conserved in a large family of amino acid transport proteins, and site-directed mutagenesis identifies them as being essential for transport activity. It is postulated that these residues together with E110 in transmembrane span 3 may be involved in a proton relay system.


Effect of physiological and pharmacologically induced thymus involution on the immunoreactivity in C57BL mice.
The effect of physiological and pharmacologically induced thymus involution was studied in 12-week-old female C57BL mice. Thymus involution was estimated by measurement of the thymus weight and the ability of thymocytes to induce a graft-versus-host (GvH) reaction at 48 h after delivery or drug administration in comparison with control (virgin, saline-treated) mice. The thymus weight and immunoreactivity of thymocytes after delivery were reduced in a statistically significant manner by ca. 80 and 75%, respectively. On the other hand, hydrocortisone administration decreased the thymus weight (by ca. 60%), but did not change the ability of thymocytes to induce a GvH reaction. Cyclophosphamide administration significantly reduced both the thymus weight and the reactivity of thymocytes. The present study suggests that the transient thymus involution observed after delivery, connected with a loss of the ability of thymocytes to induce a GvH reaction, cannot be explained merely by elimination of a steroid-sensitive cortical cell population, since the GvH reactivity of thymocytes was preserved in hydrocortisone-treated mice.


Cell type and spatial location dependence of cytoplasmic viscosity measured by time-resolved fluorescence microscopy.
Information on the cell type and spatial location dependence of cytoplasmic viscosity would be very useful in understanding some of the processes occurring in the cell. For this purpose, fluorescent dye kiton red (sulforhodamine B) was loaded into a variety of cells such as Swiss 3T3 fibroblasts, human mononuclear cells, Sarcoma-180 tumor cells, Chinese hamster ovary cells, plant cells from Digitalis lanata, stamen hair cells of Tradescantia, and guard mother cells of Allium cepa. Space-resolved measurements of cytoplasmic viscosity were carried out by using an experimental set-up wherein a picosecond laser system was coupled with an epifluorescence microscope. The spatial resolution of this set-up was approximately 1.0 micron, and reliable dynamic fluorescence measurements could be obtained from 10(2) to 10(3) fluorescent molecules. Fluorescence lifetime measurements showed that a large fraction (approximately 70%) of kiton red was in the free form. Fluorescence anisotropy decay of kiton red in cells was analyzed by a two population (free and bound) model. The microviscosity of cytoplasm was estimated from the anisotropy decay kinetics of the free probe. It was found that the cytoplasmic viscosity is dependent on both the cell type and spatial location within a cell. Furthermore, both the average value of viscosity and spatial variation within a cell were larger in the plant cells when compared to the animal cells. Model studies in various simpler systems have shown that the higher viscosity observed in some part of the cell could be due to either physical restriction and/or the presence of high concentrations of small solutes and macromolecules.


Lymphomas of the female genital tract: a study of 186 cases and review of the literature.
Malignant lymphomas in the female genital tract are rare, and those arising from this tissue system are extremely uncommon. Most pertinent reports lack clear references to the accepted classifications or failed to apply immunomarkers and molecular techniques for a reliable diagnosis. We analyzed a large group of patients with primary and secondary lymphomas of the female genital tract classified on the basis of the recent WHO consensus. A total of 186 patients with malignant lymphoma detected in the female genital tract were selected from the files of the Kiel Lymphoma Registry covering the period of 1974 to 2004. Stringent criteria were applied to separate systemic versus secondary lymphomas. All cases were reviewed on the basis of conventionally stained sections, relevant immunohistochemistry using the alkaline phosphatase/anti-alkaline phosphatase technique, and clinical information, as far as available. When required, gene rearrangement analysis was performed, including TCR-gamma chain gene and the three FR fragments of the IgG heavy chain gene. In addition, typical chromosomal translocations were detected by means of the FISH technique to verify the diagnosis, where needed. Thirty-seven percent of the cases were systemic lymphomas and 63% were mostly extranodal lymphomas primary to the female genital tract. The adnexa were involved in 87 cases, followed by uterine corpus in 23 cases, uterine cervix in 17 cases, portio in 9 cases, vagina in 11 cases, and vulva including clitoris in 8 cases. In 31 cases, two or more adjacent sites were involved. In both (primary and secondary) groups, the adnexa were the prevailing site of involvement. As expected, the overwhelming majority of cases were of B phenotype. The most frequent type of lymphoma proved to be diffuse large B-cell lymphoma, closely followed by follicular lymphoma, including all 3 grades of malignancy. Burkitt lymphoma showed a rather similar frequency. Marginal zone lymphoma occurred exclusively as primary lesions in the uterine mucosa. Lymphoplasmacytic lymphoma was restricted to the vulvo-vaginal area and occurred in women over 60 years of age. In conclusion, our study provides a thorough overview of various types of lymphoma affecting the female genital tract primarily or secondarily, which were classified on the basis of a widely accepted WHO classification. Although quite rare, our report should remind the pathologist of considering malignant lymphomas while reading biopsies taken from female genital organ.


Sex estimation from sternal measurements using multidetector computed tomography.
We aimed to show the utility and reliability of sternal morphometric analysis for sex estimation.Sex estimation is a very important step in forensic identification. Skeletal surveys are main methods for sex estimation studies. Morphometric analysis of sternum may provide high accuracy rated data in sex discrimination. In this study, morphometric analysis of sternum was evaluated in 1 mm chest computed tomography scans for sex estimation. Four hundred forty 3 subjects (202 female, 241 male, mean age: 44 ± 8.1 [distribution: 30-60 year old]) were included the study. Manubrium length (ML), mesosternum length (2L), Sternebra 1 (S1W), and Sternebra 3 (S3W) width were measured and also sternal index (SI) was calculated. Differences between genders were evaluated by student t-test. Predictive factors of sex were determined by discrimination analysis and receiver operating characteristic (ROC) analysis. Male sternal measurement values are significantly higher than females (P < 0.001) while SI is significantly low in males (P < 0.001). In discrimination analysis, MSL has high accuracy rate with 80.2% in females and 80.9% in males. MSL also has the best sensitivity (75.9%) and specificity (87.6%) values. Accuracy rates were above 80% in 3 stepwise discrimination analysis for both sexes. Stepwise 1 (ML, MSL, S1W, S3W) has the highest accuracy rate in stepwise discrimination analysis with 86.1% in females and 83.8% in males. Our study showed that morphometric computed tomography analysis of sternum might provide important information for sex estimation.


Subpopulations of Langerhans' cells in cervical neoplasia.
Multiple markers were used to count Langerhans' cells in the cervix. In the normal cervix, thymocyte antigen (T6) and adenosine triphosphatase (ATPase) demonstrated the largest population of Langerhans' cells. MHC Class II positive cells were equivalent to 60%, and S100 positive cells were equivalent to 35% of T6 or ATPase positive cells. Whereas Langerhans' cells demonstrated by T6, ATPase, and MHC Class II antigen were evenly distributed throughout the epithelium, the S100 positive cells were seen predominantly near lymphocytic aggregates and capillaries. In human papillomavirus infection and cervical intraepithelial neoplasia the numbers of T6, ATPase, or MHC Class II positive Langerhans' cells were reduced by 60% but the S100 positive cells were almost completely depleted. These findings suggested that there were different subpopulations of Langerhans' cells in the cervical epithelium. The depletion of Langerhans' cells, particularly the selective depletion of the S100 positive subpopulation, might cause a localized immunodeficiency that impairs immune surveillance and the cell-mediated immune response to human papillomavirus infection and cervical intraepithelial neoplasia.


B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes.
Therapy to lower homocysteine with B vitamins does reduce the risk of stroke, if not myocardial infarction. The apparent lack of efficacy of vitamin therapy in most of the large clinical trials was probably determined by the failure to take account of the metabolic deficiency of vitamin B12, which is very common and often missed, and by the failure to take account of impaired renal function. Metabolic B12 deficiency is present in 20% of people over 65 years of age, and in 30% of vascular patients above 70 years, so higher doses of B12 are needed in elderly patients. However, high-dose cyanocobalamin leads to accumulation of cyanide in patients with renal failure. B vitamin therapy is beneficial in patients with good renal function, but harmful in patients with significantly impaired renal function (a glomerular filtration rate <50). It seems likely that in patients with renal impairment, methylcobalamin should be used instead cyanocobalamin.


Structure and physical properties of SeCo1-x Mn x O3.
We describe the high-pressure (4 GPa) high-temperature (∼1100 K) synthesis of the solid solution series SeCo1-x Mn x O3 (0 < x < 1) using H2SeO4 and transition metal oxide mixtures sealed in Pt capsules. Neutron powder diffraction has been performed to determine progression of the structure across the solution. All samples crystallise with orthorhombic Pnma symmetry, and octahedral tilting is determined to increase with Mn content. SQUID magnetometry measurements were performed, and reveal that the Néel temperature shifts only by approximately 1 K over the series.


Antigen-specific activity of murine leukocyte dialysates containing transfer factor on human leukocytes in the leukocyte migration inhibition (LMI) assay.
We report on the extension of the direct leukocyte migration inhibition (LMI) test as an assay for antigen-specific activity in human leukocyte dialysates (DLE) containing transfer factor to an evaluation of antigen-specific activity in DLE prepared from inbred mice. Murine DLE was observed to cause antigen-dependent and antigen-specific effects on the inhibition of migration of nonimmune human leukocyte populations. Pulsing of nonimmune human leukocyte with DLE preparations from BALB/c and SJL mice immunized with Candida, diphtheria toxoid, and SK-SD resulted in their inhibition of migration in the presence of the respective antigens. The antigen-specific activity in murine DLE was found to be present in lymph node cell preparations and to be absent from spleen cell preparations of the same donors. The activity of DLE in lymph node cells was found to be present in the theta-cell enriched subpopulation of nonadherent lymphocytes after passage through nylon wool columns. The antigen-specific activity of murine DLE, as we have reported for human DLE, was found to reside in the < 3500 dalton dialysis fraction and not in the < 3500 dalton fraction. We conclude that nonimmune human leukocytes in the LMI test provide a suitable assay for the detection of antigen-specific activity in murine DLE as well as that in human DLE. Additionally, murine DLE is active across species barriers and appears to share properties with human DLE.


Cryosurgery of the prostate: techniques and indications.
Cryosurgical ablation of the prostate (CSAP) is indicated for patients with high-stage and high-grade tumors, patients with recurrent/persistent carcinoma of the prostate after external radiation therapy or brachytherapy, and others. At Allegheny General Hospital, CSAP is performed as follows: the patient is prepped in an exaggerated lithotomy position; a volumetric study of the gland is obtained with transrectal ultrasound; 5 to 15 cryoneedles are placed (in three to five horizontal rows) through a 17-gauge, stepper-mounted template; a cystoscopy is performed; and a urethral warming catheter is introduced. The rows of cryoneedles are then activated from anterior to posterior, and generally two freeze-thaw cycles are used. In longer glands, a pullback of the cryoneedles might be needed to completely cover the apical portion of the gland. The skills required for CSAP are identical to those required for brachytherapy needle placement, thus the training required for physicians already proficient in brachytherapy is minimized.


Effects of angiotensin-converting enzyme inhibitors on the vascular response to norepinephrine.
The effects of three types of angiotensin-converting enzyme inhibitor, SQ 14225 (captopril), SQ 20881 (teprotide) and SA 446 (Santen, Osaka, Japan), on the vascular contraction induced by norepinephrine were studied in the perfused rat mesenteric vascular bed. (1) SQ 14225 attenuated in the vascular contraction induced by norepinephrine, but SQ 20881 and SA 446 revealed no effect on vascular reactivity. (2) The effect of SQ 14225 was not altered in the presence of bradykinin or angiotensin II in the perfusate. On the basis of these results it is suggested that the attenuating effect on the vascular response to norepinephrine may be limited to SQ 14225 and that its effect is not mediated through the renin-angiotensin or kallikrein-kinin system.


Origins of Uralic-speaking populations:craniological evidence.
Data on 55 modern cranial samples representing Uralic and other Eurasian populations were subjected to canonical variate (CV) and principal component (PC) analysis for 6 nonmetric and 14 metric traits, respectively. While PC1 and CV1 reveal strong east-to-west gradients among the Uralians, PC2 and CV2 separate most of them from the remaining groups, suggesting that they have descended from an ancestral proto-Uralian population. The biologically "Uralic" features survive in modern Uralic groups despite the fact that the initial split was followed by a long period of hybridization with widely dissimilar people. Our results confirm that the ancestors of many Turkish-speaking groups as well as the Yukaghirs belonged to the proto-Uralic community.


Amorphous Ni-Fe-Se hollow nanospheres electrodeposited on nickel foam as a highly active and bifunctional catalyst for alkaline water splitting.
Developing earth-abundant highly efficient catalysts for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is indispensable for the widespread implementation of electrochemical water splitting to store renewable energy. Herein, amorphous bimetallic selenide (Ni-Fe-Se) hollow nanospheres electrodeposited on nickel foam (Ni-Fe-Se/NF) are developed as a bifunctional catalyst for the HER and OER. The HER and OER bifunctional activity of Ni-Fe-Se/NF outperforms those of monometallic Ni-Se/NF and Fe-Se/NF owing to the synergy of Ni and Fe in Ni-Fe-Se/NF. Moreover, the amorphous hollow spherical morphology of Ni-Fe-Se/NF increases the active site density and facilitates the mass transfer of electrolytes and H2/O2 products. Ni-Fe-Se/NF drives a current density of 10 mA cm-2 with an overpotential of ∼85 mV for the HER and 100 mA cm-2 with an overpotential of ∼222 mV for the OER. As the HER and OER bifunctional catalyst, Ni-Fe-Se/NF can split alkaline water with total voltages of ∼1.52 V and ∼1.66 V at 10 mA cm-2 and 100 mA cm-2, respectively, and remain stable over 50 hours of operation in 1 M KOH.


Exact Density Functional Obtained via the Levy Constrained Search.
A stochastic minimization method for a real-space wave function, Ψ(r1, r2...r n), constrained to a chosen density, ρ(r), is developed. It enables the explicit calculation of the Levy constrained search, F[ρ] = minΨ→ρ⟨Ψ| T̂ + V̂ ee|Ψ⟩, which gives the exact functional of density functional theory. This general method is illustrated in the evaluation of F[ρ] for densities in one dimension with a soft-Coulomb interaction. Additionally, procedures are given to determine the first and second functional derivatives, δ F/δρ(r) and δ2 F/[δρ(r)δρ(r')]. For a chosen external potential, v(r), the functional and its derivatives are used in minimizations over densities to give the exact energy, E v, without needing to solve the Schrödinger equation.


Decreased IGF1R attenuates senescence and improves function in pancreatic β-cells.
The enhanced β-cell senescence that accompanies insulin resistance and aging contributes to cellular dysfunction and loss of transcriptional identity leading to type 2 diabetes (T2D). While senescence is among the 12 recognized hallmarks of aging, its relation to other hallmarks including altered nutrient sensing (insulin/IGF1 pathway) in β-cells is not fully understood. We previously reported that an increased expression of IGF1R in mouse and human β-cells is a marker of older β-cells; however, its contribution to age-related dysfunction and cellular senescence remains to be determined. In this study, we explored the direct role of IGF1R in β-cell function and senescence using two independent mouse models with decreased IGF1/IGF1R signaling: a) Ames Dwarf mice (Dwarf +/+), which lack growth hormone and therefore have reduced circulating levels of IGF1, and b) inducible β-cell-specific IGF1R knockdown (βIgf1rKD) mice. Compared to Dwarf+/- mice, Dwarf+/+ mice had lower body and pancreas weight, lower circulating IGF1 and insulin levels, and lower IGF1R and p21Cip1 protein expression in β-cells, suggesting the suppression of senescence. Adult βIgf1rKD mice showed improved glucose clearance and glucose-induced insulin secretion, accompanied by decreased p21Cip1 protein expression in β-cells. RNA-Seq of islets isolated from these βIgf1rKD mice revealed the restoration of three signaling pathways known to be downregulated by aging: sulfide oxidation, autophagy, and mTOR signaling. Additionally, deletion of IGF1R in mouse β-cells increased transcription of genes important for maintaining β-cell identity and function, such as Mafa, Nkx6.1, and Kcnj11, while decreasing senescence-related genes, such as Cdkn2a, Il1b, and Serpine 1. Decreased senescence and improved insulin-secretory function of β-cells were also evident when the βIgf1rKD mice were fed a high-fat diet (HFD; 60% kcal from fat, for 5 weeks). These results suggest that IGF1R signaling plays a causal role in aging-induced β-cell dysfunction. Our data also demonstrate a relationship between decreased IGF1R signaling and suppressed cellular senescence in pancreatic β-cells. Future studies can further our understanding of the interaction between senescence and aging, developing interventions that restore β-cell function and identity, therefore preventing the progression to T2D.


Assessment of inflammatory activity in Crohn's disease.
Complaints or symptoms of Crohn's disease can be due either to intestinal inflammation or to anatomical abnormalities such as strictures, fistulas and previous intestinal resection, or to a combination of these factors. Since anti-inflammatory or immunosuppressive drugs are only effective in reducing inflammation, assessment of the presence or absence of active inflammation is of great clinical importance. Several disease activity indices have been developed, but none is able to accurately assess inflammatory activity in Crohn's disease. Furthermore, blood parameters of inflammation, such as ESR, leukocytes, thrombocytes and albumin, are not bowel-specific. In contrast, faecal inflammatory parameters are specific for intestinal inflammation. Preliminary results from our laboratory suggest that measurement of intestinal alpha 1-antitrypsin clearance is a sensitive and bowel-specific indicator of active inflammation in Crohn's disease. This inexpensive, safe and patient-friendly measurement deserves a prominent place, not only in drug trials but also in clinical management of patients with Crohn's disease.


Primary malignant lymphoma of the mandible.
From 1945 through 1985, 32 cases of primary lymphoma of bone were treated at the University of Iowa Hospitals and Clinics. Sixteen cases (50%) demonstrated the lesion in the long tubular bones with a predilection for the lower and upper extremities. The frequently involved flat bones (six cases) were the bones of the pelvis. There were only three cases (9%) where the mandible was the primary site. In this report, the literature is reviewed and three cases with primary lymphoma of the mandible are presented.


Global and Simultaneous Hypothesis Testing for High-Dimensional Logistic Regression Models.
High-dimensional logistic regression is widely used in analyzing data with binary outcomes. In this paper, global testing and large-scale multiple testing for the regression coefficients are considered in both single- and two-regression settings. A test statistic for testing the global null hypothesis is constructed using a generalized low-dimensional projection for bias correction and its asymptotic null distribution is derived. A lower bound for the global testing is established, which shows that the proposed test is asymptotically minimax optimal over some sparsity range. For testing the individual coefficients simultaneously, multiple testing procedures are proposed and shown to control the false discovery rate (FDR) and falsely discovered variables (FDV) asymptotically. Simulation studies are carried out to examine the numerical performance of the proposed tests and their superiority over existing methods. The testing procedures are also illustrated by analyzing a data set of a metabolomics study that investigates the association between fecal metabolites and pediatric Crohn's disease and the effects of treatment on such associations.


[Arterial hypertension in the French Caribbean regions: gender related differences].
Arterial hypertension is a frequent disease, responsible for a significant morbidity, in the French Caribbean regions. Today, epidemiological studies on this topic remain few. To analyse the prevalence, awareness, treatment and control of arterial hypertension in the French Caribbean regions. Analysis of the INHAPAG cohort (Incidence of Arterial Hypertension in the Working population Antillo-Guyanaise) carried out in 2001, and including 6113 active subjects recruited in Guadeloupe, Martinique and Guyana. The procedure of diagnosis of arterial hypertension comprises two visits, with a series of three measurements of the blood pressure at each visit. Prevalence of hypertension is estimated to be 18.9% among women and 19.5% among men. The rates of treatment are higher among women (74.8 vs 34.4%) than among men, resulting in a much better control rate (61.3% vs 38.6% among men). An analysis of factors associated with the presence of arterial hypertension shows a noxious role of low education level among women. Our study finds marked differences between women and men in the treatment and control of arterial hypertension and underline the need for improving blood pressure management of the latter.


Renal response to lower body positive pressure produced by military anti-shock trousers.
Military anti-shock trousers (MAST) are extensively used in the management of various forms of clinical shock and are presumed to produce their antihypotensive effect by the autotransfusion of blood from the lower extremities. In the present studies we documented the renal response to (1) four hours of recumbency; (2) 4 h of MAST inflation at a pressure of 45 mm Hg over the lower extremities and 15 mm Hg over the abdomen, and (3) 4 h of thermoneutral head-out water immersion in a group of salt replete normal subjects. Similar studies were performed in a group of adults with nephrotic syndrome and edema. In both normal and nephrotic subjects only water immersion produced a natriuresis that was significantly greater than during recumbency. The mean natriuresis following MAST inflation in normal subjects was somewhat greater than that during recumbency but the difference was neither consistent nor statistically significant. We conclude that MAST inflation does not lead to central translocation of more fluid than what would be expected from the assumption of recumbent posture. Thus, MAST are unlikely to be of therapeutic benefit in the relief of edema in patients with nephrotic syndrome and a critical evaluation of their mechanisms of action in the management of hypotension is required.


Coach-led prevention programs are effective in reducing anterior cruciate ligament injury risk in female athletes: A number-needed-to-treat analysis.
The purpose of this study was to determine whether the effectiveness of an anterior cruciate ligament (ACL) prevention program is impacted by the individual(s) directing the program. A number-needed-to-treat analysis compared the effectiveness of injury prevention measures when either directed by a coach or a mixed leadership group consisting of coach and healthcare providers. Eleven studies were included for analysis. Number-needed-to-treat and relative risk reduction (RRR) were calculated for each study and data sets were pooled based on the intervention leader. Quality of evidence was determined by assessing individual studies (PEDro score x¯=4.55±1.97, range=2-7), applying the Oxford Centre for Evidence-Based Medicine Levels of Evidence (CEBM=2a), and the Strength of Recommendation Taxonomy (SORT=Level B). The mixed leadership group studies' RRR=48.2% (95% confidence interval (CI)=22-65) and a number-needed-to-benefit of 120 (CI=73-303) while the coach-led group's RRR=58.4% (CI=40-71) and a number-needed-to-benefit=133 (CI=96-217). These results demonstrate that a coach-led ACL injury prevention program approach is as effective as a mixed group leadership approach. Coach-led prevention programs can be more widely implemented; however, it is imperative to ensure adequate training is in place prior to implementation of such intervention.


Ultrashort pulse generation by semiconductor mode-locked lasers at 760 nm.
We demonstrate the first semiconductor mode-locked lasers for ultrashort pulse generation at the 760 nm waveband. Multi-section laser diodes based on an AlGaAs multi-quantum-well structure were passively mode-locked, resulting in the generation of pulses at around 766 nm, with pulse durations down to ~4 ps, at pulse repetition rates of 19.4 GHz or 23.2 GHz (with different laser cavity lengths of 1.8 mm and 1.5 mm, respectively). The influence of the bias conditions on the mode-locking characteristics was investigated for these new lasers, revealing trends which can be ascribed to the interplay of dynamical processes in the saturable absorber and gain sections. It was also found that the front facet reflectivity played a key role in the stability of mode-locking and the occurrence of self-pulsations. These lasers hold significant promise as light sources for multi-photon biomedical imaging, as well as in other applications such as frequency conversion into the ultraviolet and radio-over-fibre communications.


Study of the microbial ecology of cold-smoked salmon during storage at 8 degrees C.
Microbiological, chemical and sensory changes in cold-smoked salmon were studied during 5 weeks of vacuum storage at 8 degrees C. The aerobic 20 degrees C viable count reached its maximum level after 6 days (3 x 10(6) cfu g-1) however, the shelf-life of the product was estimated to be 2 or 3 weeks by the panellists, confirming that there is no correlation between those two factors. Acid, pungent, sour and rancid odours and flavours and pasty texture were the main spoilage characteristics. Trimethylamine did not play a major role in the spoilage mechanisms as only small amounts were produced. Two-hundred and seventy strains were collected over the storage period, purified and characterized. During the first 2 weeks, Gram-negative bacteria were dominant, mainly represented by S. putrefaciens immediately after the smoking process and then P. phosphoreum. Aeromonas spp. were present throughout the storage but in smaller amounts. Gram-negative bacteria then progressively decreased while Gram-positive bacteria, dominated by lactic acid bacteria (LAB), became by far the most common variety found. Carnobacterium piscicola was widely represented (97/155 LAB isolates). A diversification was observed at the end of the storage, with the appearance of L. farciminis, L. sake and L. alimentarius. Occurrence of yeasts and moulds was quite rare. Spoilage potential of the strains was tested on a sterile smoked salmon extract juice. Shewanella putrefaciens, Aeromonas spp. and Brachothrix spp. produced strong off-odours while most of the LAB and P. phosphoreum seemed not to be involved in spoilage.


Torquoselectivity in the Nazarov reactions of allenyl vinyl ketones.
Nazarov reactions mediated by BF3-etherate of a series of carbon-substituted allenyl vinyl ketones provided intermediates in which substituents on the termini of the allenes had rotated away from the vinyl moieties, and these intermediates were trapped by (4 + 3)-cyclizations. A computational examination of the torquoselectivity of these Nazarov reactions confirmed a kinetic preference for the observed isomers and pointed to steric interactions and the degree of allene deformation as significant factors in determining the torquoselectivity. The study also suggested that the high proportion of one geometrical isomer in the Nazarov products might also be due to some preferential trapping of the major Nazarov intermediate.


An enzyme immunoassay procedure for cancer antigen 125 evaluated.
The performance of a new enzyme immunoassay (EIA) procedure (Abbott Labs.) for cancer antigen 125 (CA 125) met or exceeded the manufacturer's claims for all analytical variables examined. Overall correlation with results obtained with a radioimmunoassay (RIA) were good. However, near the decision thresholds typically chosen to define a positive result for ovarian carcinoma, EIA results were 10 to 20 arbitrary units/mL less than the RIA results. At specific decision thresholds, therefore, the sensitivities and specificities of the EIA and RIA procedure differed. Adjusting the decision thresholds gave a similar optimum efficiency for each procedure: EIA, 82.9% (decision threshold, 35 units/mL); RIA, 83.4% (decision threshold, 54 units/mL). Receiver-operating characteristic curves showed that the two procedures' ability to distinguish patients with active ovarian carcinoma from those with disease in remission was the same.


Loss of AT-rich interactive domain 1A expression in gastrointestinal malignancies.
AT-rich interactive domain 1A (ARID1A) has recently been identified as a novel tumor suppressor in various tumor types. This study was designed to explore the clinical relevance and prognostic impact of ARID1A expression loss in colorectal cancer (CRC) and gastric cancer (GC). Immunohistochemistry for ARID1A was performed using tissue microarray blocks containing 196 CRCs and 275 GCs, along with paired normal mucosa. Data on clinicopathologic variables and oncologic outcomes of patients were collected and analyzed. We identified 6.1% (12/196) CRC and 8.0% (22/275) GC cases showing loss of ARID1A expression. Expression of ARID1A in paired mucosal epithelial cells was normal in all patients. Loss of ARID1A expression was significantly correlated with negative lymphatic invasion (p = 0.003) in CRC, with large tumor size (p = 0.037) in GC, and with expanding tumor border in both tumor types (CRC, p = 0.010; GC, p = 0.031). However, no association was evident between ARID1A expression and 5-year overall survival in both tumor types. Loss of ARID1A expression is uncommon and not associated with oncologic outcome but may be related to less invasive clinicopathologic features in CRC and GC. Further studies with a larger number of subjects are needed to establish the possible prognostic impact of ARID1A expression loss.


Anticipatory stress influences decision making under explicit risk conditions.
Recent research has suggested that stress may affect memory, executive functioning, and decision making on the basis of emotional feedback processing. The current study examined whether anticipatory stress affects decision making measured with the Game of Dice Task (GDT), a decision-making task with explicit and stable rules that taps both executive functioning and feedback learning. The authors induced stress in 20 participants by having them anticipate giving a public speech and also examined 20 comparison subjects. The authors assessed the level of stress with questionnaires and endocrine markers (salivary cortisol and alpha-amylase), both revealing that speech anticipation led to increased stress. Results of the GDT showed that participants under stress scored significantly lower than the comparison group and that GDT performance was negatively correlated with the increase of cortisol. Our results indicate that stress can lead to disadvantageous decision making even when explicit and stable information about outcome contingencies is provided.


Performance of pulse palpation compared to one-lead ECG in atrial fibrillation screening.
The 2020 European Society of Cardiology atrial fibrillation guidelines recommend opportunistic screening for atrial fibrillation by pulse taking or ECG rhythm strip in those aged over 65 years. We aimed to compare the diagnostic accuracy of pulse palpation to ECG rhythm strip when screening for atrial fibrillation. A secondary aim was to investigate whether participants with palpitations were more likely to be diagnosed with new atrial fibrillation. The study population were 75/76 year old individuals that participated in the STROKESTOP II study, a Swedish screening study for atrial fibrillation. Pulse palpation of the radial pulse for 30 sec was performed by healthcare professionals and recorded as regular or irregular. Thereafter a 30-sec single-lead ECG was registered. Patients were asked also if they had a history of palpitations. Of the 6159 participants included in the study, 461 (7.5%) had irregular pulse. Twenty-two (4.8%) of those with irregular pulse were diagnosed with atrial fibrillation on single-lead ECG rhythm strip. Among those with regular pulse, 6 (0.1%) cases of new atrial fibrillation were found. The sensitivity of the pulse palpation test was 78.6% and positive predictive value 4.8%. The proportion of newly diagnosed atrial fibrillation was not different between those with and without history of palpitations. Pulse palpation was inferior to single-lead ECG when screening for atrial fibrillation. We therefore advocate the use of single-lead ECG rather than pulse palpation when screening for atrial fibrillation. Palpitations did not predict atrial fibrillation.


Retroperitoneal malignant peripheral nerve sheath tumor replacing an absent kidney in a child.
Malignant peripheral nerve sheath tumors (MPNSTs) are nonrhabdomyosarcoma soft tissue sarcomas with rare occurrence in children specially in the retroperitoneum. We describe a young child who presented with an abdominal mass. Both ultrasound and computed tomography revealed a large right-sided abdominal mass in the anatomic place of right kidney, while no kidney or ureter was observed at that side. He underwent surgical resection of the tumor with a primary impression of Wilms tumor. To the authors' knowledge, this is the first case of retroperitoneal malignant peripheral nerve sheath tumor and absent kidney. This case suggests the very rare probability of association of MPNSTs in children with genitourinary tract anomalies such as renal agenesis.


Reproductive phenology is a repeatable, heritable trait linked to the timing of other life-history events in a migratory marine predator.
Population-level shifts in reproductive phenology in response to environmental change are common, but whether individual-level responses are modified by demographic and genetic factors remains less well understood. We used mixed models to quantify how reproductive timing varied across 1772 female southern elephant seals (Mirounga leonina) breeding at Marion Island in the Southern Ocean (1989-2019), and to identify the factors that correlate with phenological shifts within and between individuals. We found strong support for covariation in the timing of breeding arrival dates and the timing of the preceding moult. Breeding arrival dates were more repeatable at the individual level, as compared with the population level, even after accounting for individual traits (wean date as a pup, age and breeding experience) associated with phenological variability. Mother-daughter similarities in breeding phenology were also evident, indicating that additive genetic effects may contribute to between-individual variation in breeding phenology. Over 30 years, elephant seal phenology did not change towards earlier or later dates, and we found no correlation between annual fluctuations in phenology and indices of environmental variation. Our results show how maternal genetic (or non-genetic) effects, individual traits and linkages between cyclical life-history events can drive within- and between-individual variation in reproductive phenology.


Elevated trace element concentrations in malignant breast tissues.
In vitro neutron activation analysis (NAA) was performed on malignant and adjacent normal tissue from 46 human female breast tumours. The objective was to investigate the chemical environment of the tissues within which microcalcifications develop and to develop a method for discrimination between malignant and normal breast tissue. The elements Al, Br, Ca, Cl, Co, Cs, Fe, K, Mn, Na, Rb and Zn were significantly higher in the cancer tissues (all p < 0.001; except for Co, p < 0.003, Wilcoxon signed-ranks test). In addition, a significant correlation (0.80, Spearman rank correlation) was found for Rb and Zn in tumour tissues. Present results are supported by the findings of others. The relevance of elevated concentrations of these elements in cancer breast tissue remains a matter of conjecture. Evidence suggests that there is a connection both with increased cellular activity and blood supply and the formation of microcalcifications in malignant breast tissues. This study suggests an association between the elemental composition of breast tissues and the formation of breast particles. That is, elevations of elemental concentration and clustered calcifications in breast are possibly related.


Stochastic interplay between mutation and recombination during the acquisition of drug resistance mutations in human immunodeficiency virus type 1.
The emergence of drug resistance mutations in human immunodeficiency virus (HIV) has been a major setback in the treatment of infected patients. Besides the high mutation rate, recombination has been conjectured to have an important impact on the emergence of drug resistance. Population genetic theory suggests that in populations limited in size recombination may facilitate the acquisition of beneficial mutations. The viral population in an infected patient may indeed represent such a population limited in size, since current estimates of the effective population size range from 500 to 10(5). To address the effects of limited population size, we therefore expand a previously described deterministic population genetic model of HIV replication by incorporating the stochastic processes that occur in finite populations of infected cells. Using parameter estimates from the literature, we simulate the evolution of drug-resistant viral strains. The simulations show that recombination has only a minor effect on the rate of acquisition of drug resistance mutations in populations with effective population sizes as small as 1,000, since in these populations, viral strains typically fix beneficial mutations sequentially. However, for intermediate effective population sizes (10(4) to 10(5)), recombination can accelerate the evolution of drug resistance by up to 25%. Furthermore, a reduction in population size caused by drug therapy can be overcome by a higher viral mutation rate, leading to a faster evolution of drug resistance.


The plant cell cycle: Pre-Replication complex formation and controls.
The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes.


Tailoring a Dynamic Metal-Polymer Interaction to Improve Catalyst Selectivity and Longevity in Hydrogenation.
Controlling metal-support interactions is important for tuning the catalytic properties of supported metal catalysts. Here, premade Pd particles are supported on stable polymers containing different ligating functionalities to control the metal-polymer interactions and their catalytic properties in industrially relevant acetylene partial hydrogenation. The polymers containing strongly ligating groups (e.g., Ar-SH and Ar-S-Ar) can form a polymer overlayer on the Pd surface, which enables selective acetylene adsorption and partial hydrogenation to ethylene without deactivation. In contrast, polymers with weakly ligating groups (e.g., Ar-O-Ar) do not form an overlayer, resulting in non-selective hydrogenation and fast deactivation, similar to Pd catalysts on conventional inorganic supports. The results imply that tuning the metal-polymer interactions via rational polymer design can provide an efficient way of synthesizing selective and stable catalysts for hydrogenation.


Optimization of radiation protection for the control of occupational exposure in Ghana.
Investigation of the optimization of protection of occupational exposed workers (OEWs) in Ghana had been carried out on the three practices in the country, namely medical applications, industrial radioisotope applications and research and education from 2002 to 2007. Mean annual effective dose and collective effective dose were estimated from dosimetry records from the Radiation Protection Institute of those occupationally exposed from 2002 to 2007. The mean annual effective dose estimated for about 650 OEWs per year ranged from 0.42 to 0.68 mSv compared with a global value of 0.5 mSv estimated by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR 2008 Report). This implies that efforts should still be made to institute as low as reasonably achievable culture in most practices in Ghana even though trend of doses incurred was low. The collective effective dose for this same period estimated ranged from 0.26 to 0.47 man Sv. A reference monetary value of the man sievert was estimated using the human capital approach for each year from 2002 to 2009; it ranged from 172 to 22 US $ per man Sv, which provided a basis for estimating the cost of averting a unit collective effective dose of 1 man Sv. This value could not be used for quantitative optimization since the range of mean annual effective dose estimated was below 1 mSv.


Secretion of long Abeta-related peptides processed at epsilon-cleavage site is dependent on the alpha-secretase pre-cutting.
Abeta is the major component of amyloid in the brain in Alzheimer's disease and is derived from Alzheimer amyloid precursor protein (APP) by sequential proteolytic cleavage involving alpha-, beta- and gamma-secretase. Recently, gamma-secretase was shown to cleave near the cytoplasmic membrane boundary of APP (called the epsilon-cleavage), as well as in the middle of the membrane domain (gamma-cleavage). However, the precise relationship between gamma- and epsilon-cleavage is still unknown. In this paper, I analyzed Abeta-related peptides using immunoprecipitation and liquid chromatography ion trap mass spectrometer and found some long Abeta-related peptides, starting at Abeta residues 16Lys-23Asp and ending at 43Thr-52Leu, in the culture media of COS-1 cells and in human brain extract. These results indicated that longer Abeta-related peptides cleaved at epsilon-cleavage site were secreted under normal conditions and were dependent on the alpha-secretase cleavage products.


Monocyte-dependent, serum-borne suppressor of induction of lymphokine-activated killer cells in lymphocytes from melanoma patients.
Both phytohemagglutinin-induced cytotoxicity and recombinant-interleukin-2 (rIL-2)-induced lymphokine-activated killer (LAK) activity against noncultured melanoma cells were significantly reduced when peripheral blood mononuclear cells (PBMC) from patients with metastatic melanoma were incubated in RPMI medium 1640 and 10% autologous human serum instead of 10% fetal calf serum, while serum from either healthy donors or patients with primary melanoma did not affect the level of cytotoxicity. The serum-mediated suppression was not restricted by major histocompatibility complex and was time-dependent. Addition of 10% human serum from the patients with metastatic melanoma [HS-Pt(m)] to the culture of PBMC with rIL-2 at the same time or 1 day after incubation significantly inhibited LAK activity. However, addition of 10% HS-Pt(m) 2 or 3 days after incubation did not inhibit LAK activity. Incubation of PBMC for 2 h with a high dose (10(4) U/ml) of rIL-2 in the presence of 10% HS-Pt(m), followed by incubation in the absence of either rIL-2 or HS-Pt(m), did not affect LAK cell activity. These results suggest that HS-Pt(m) inhibits the early stage of LAK cell differentiation, rather than the binding of rIL-2 to PBMC or a later stage in the differentiation. In contrast to PBMC, monocyte-depleted peripheral blood lymphocytes exhibited comparable levels of LAK activity when cultured with rIL-2 either in 10% fetal calf serum, 10% human serum from healthy donors or 10% HS-Pt(m). Addition of purified autologous monocytes to the culture of monocyte-depleted peripheral blood lymphocytes with rIL-2 suppressed LAK cell induction when 10% HS-Pt(m) was present. Thus serum-mediated suppression of LAK cell induction is largely dependent on the presence of monocytes, which may produce a secondary inhibitor that acts on lymphocytes. Addition of indomethacin to the culture did not reverse this monocyte-dependent serum-mediated suppression in a majority of cases, suggesting that prostaglandin E2 does not have a major role in the suppression.


In Situ Visualization of the Pinning Effect of Planar Defects on Li Ion Insertion.
Longevity of Li ion batteries strongly depends on the interaction of transporting Li ions in electrode crystals with defects. However, detailed interactions between the Li ion flux and structural defects in the host crystal remain obscure due to the transient nature of such interactions. Here, by in situ transmission electron microscopy and density function theory calculations, we reveal how the diffusion pathways and transport kinetics of a Li ion can be affected by planar defects in a tungsten trioxide lattice. We uncover that changes in charge distribution and lattice spacing along the planar defects disrupt the continuity of ion conduction channels and dramatically increase the energy barrier of Li diffusion, thus, arresting Li ions at the defect sites and twisting the lithiation front. The atomic-scale understanding holds critical implications for rational interface design in solid-state batteries and solid oxide fuel cells.


[Screening and identification of endophytic fungi with growth promoting effect on Dendrobium officinale].
The endophytic fungi with plant growth promoting effects were screened by co-culture of each endophytic fungus and seedlings of Dendrobium officinale. Anatomical features of the inoculated roots were studied by paraffin sectioning. Morphological characteristics and rDNA ITS1-5. 8S-ITS2 sequences were applied for the taxonomy of endophytic fungi. The results showed that 8 strains inoculated to D. officinale seedlings greatly enhanced plant height, stem diameter, new roots number and biomass. According to the anatomical features of the inoculated roots, each fungus could infect the velamina of seedlings. The hyphae or pelotons were existed in the exodermis passage cells and cortex cells. The effective fungi could not infect the endodermis and vascular bundle sheath, but which was exception for other fungi with harmful to seedlings. Combined with classic morphologic classification, 2 effective strains were identified which were subjected to Pestalotiopsis and Eurotium. Six species of fungi without conidiophore belonged to Pyrenochaeta, Coprinellus, Pholiota, Alternaria, Helotiales, which were identified by sequencing the PCR-amplified rDNA ITS1-5. 8S-ITS2 regions. The co-culture technology of effective endophytic fungi and plant can apply to cultivate the seedlings of D. officinale. It is feasible to shorten growth cycle of D. officinale and increase the resource of Chinese herbs.


Immunocytochemistry in the diagnosis of small blue cell tumours of childhood.
This study attempts to define a limited, cost effective, reliable primary panel of antibodies for immunohistology, as an adjunct to morphological features, for the diagnosis of Small Blue Cell Tumors (SBCT) which would be convenient for use in low resource settings to improve their diagnostic accuracy. The choice of antibodies is based on the common childhood tumors in Ibadan and limited by financial constraints and availability of antibodies. Twenty-five representative cases of previously diagnosed small blue cell tumours of childhood were selected from the file of the Department of Pathology, University College Hospital, Ibadan. The retrieved blocks were cut and stained with antibodies to desmin, leucocyte common antigen, cytokeratin, chromogranin, neuron-specific-enolase, vimentin and neurofilament using the avidin-biotin technique as previously described. Of the 25 cases studied 24 (96%) gave interpretable immunostaining reaction and the immunophenotype of these were defined. The staining quality equaled that produced on the control well-fixed positive control sections. The final diagnosis of six of the 25 cases changed based on immunostaining. Four cases previously diagnosed as lymphoma were confirmed to be rhabdomyosarcoma (3 cases) and neuroblastoma, one case each of rhabdomyosarcoma and neuroblastoma were both reclassified as lymphoma. Based on our findings, the use of a small first-line panel of antibodies to leucocyte common antigen, desmin and neuron-specific-enolase are ideal for immunohistochemical discrimination of SBCT, as an adjunct to morphology, in low-resource settings.


Introduction of liquid-based cytology and human papillomavirus testing in cervical cancer screening in Luxembourg.
In 2014, liquid-based cytology with HPV triage replaced conventional cytology. The aim of our study was to compare conventional and liquid-based cytology (LBC), estimate the prevalence of abnormal cervical cytology and high risk HPV (hrHPV) infection and their correlation, among screened women in Luxembourg. Between the first January 2013 and 31st December 2015, 315,868 cervical samples from 150,815 women (mean age 42.2 years) were investigated by the national cytology laboratory. Slides were prepared and screened according to European Guidelines. All cytological results were classified according to the Bethesda 2001 system terminology. The prevalence of abnormal cervical lesions was as follows: atypical squamous cells of undetermined significance (ASC-US), 1.3%; low-grade squamous intraepithelial lesion (LSIL), 1.9%; high-grade squamous intraepithelial lesion (HSIL), 0.4%. The detection rate of cytological lesions was significantly higher with LBC than with conventional cytology. Based on 11,838 samples with concomitant cytology and HPV testing, hrHPV was detected in 9.5, 45.3, 70.0, and 92.6% of women with negative cytology, ASC-US, LSIL, and HSIL, respectively. More cervical lesions were identified using LBC compared to conventional cytology. HrHPV infection was correlated with the severity of intraepithelial lesions. The current findings provide important information to evaluate the prevention of cervical cancer in Luxembourg and for monitoring the future impact of HPV vaccination. Diagn. Cytopathol. 2017;45:384-390. © 2017 Wiley Periodicals, Inc.