Vitamin Supplement Use in Patients With CKD: Worth the Pill Burden?
All vitamins play essential roles in various aspects of body function and systems. Patients with chronic kidney disease (CKD), including those receiving dialysis may be at increased risk of developing vitamin deficiencies due to anorexia, poor dietary intake, protein energy wasting, restricted diet, dialysis loss, or inadequate sun exposure for vitamin D. However, clinical manifestations of most vitamin deficiencies are usually subtle or undetected in this population. Testing for circulating levels are not undertaken for most vitamins except folate, B12 and 25-hydroxyvitamin D as assays may not be available or costly to do and do not always correlate with body stores. This article summarizes the more recent evidence since the last systematic review through 2016 performed for the Kidney Disease Outcome Quality Initiative (KDOQI) 2020 Nutrition Guideline update. Our aim was to review the use of vitamins supplementation in the CKD population. There are so far no randomized trials to support benefits on kidney, cardiovascular or patient-centered outcomes with any vitamin supplementation. The decision to supplement water-soluble vitamins should be individualized, taking account patients' dietary intake, nutritional status, risk of vitamins deficiency/insufficiency, CKD stage, comorbid status and dialysis loss. Nutritional vitamin D deficiency should be corrected but the supplementation dose and formulation need to be personalized, taking into consideration the degree of 25-hydroxyvitamin D deficiency, parathyroid hormone levels, CKD stage and local formulation. Routine supplementation of vitamins A and E is not supported due to potential toxicity. While more trial data are required to elucidate the roles of vitamin supplementation, all patients with CKD should undergo periodic assessment of dietary intake and aim to receive various vitamins through natural food sources and a healthy eating pattern that includes vitamin-dense foods.


Biosynthesis of platelet-activating factor in glandular gastric mucosa. Evidence for the involvement of the 'de novo' pathway and modulation by fatty acids.
The biosynthesis of platelet-activating factor (PAF), a phospholipid autocoid with potent ulcerogenic properties that is produced in secretory exocrine glands by physiological secretagogues, was assessed in microsomal preparations of glandular gastric mucosa. For this purpose, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase (EC 18.104.22.168); the enzymes of the 'de novo' pathway: 1-O-alkyl-2-lyso-sn-glycero-3-phosphate (alkyl-lyso-GP):acetyl-CoA acetyltransferase and 1-O-alkyl-2-acetyl-sn-glycerol (alkylacetyl-G):CDP-choline cholinephosphotransferase (EC 184.108.40.206); and some enzymes involved in the catabolism of PAF and lyso-PAF were assayed. Only the enzymes of the 'de novo' pathway and small amounts of PAF acetylhydrolase, phospholipase A2 and a lysophospholipase D acting on either lipids could be detected in the gastric preparations, whereas lyso-PAF:acetyl-CoA acetyltransferase activity was undetectable. The specific activity of alkyl-lyso-GP:acetyl-CoA acetyltransferase in the gastric mucosa was about one-tenth of that found in spleen microsomes and its apparent Km for acetyl-CoA was 454 microM compared with 277 microM in spleen microsomes. Glandular mucosa homogenates contained preformed PAF at a concentration of 2.7 +/- 0.7 ng equivalents of PAF (hexadecyl)/mg of protein. When gastric microsomes were incubated with micromolar concentrations of fatty acids (arachidonic, palmitic and oleic) prior to the assay of dithiothreitol (DTT)-insensitive cholinephosphotransferase, a dose-dependent reduction in the formation of PAF was observed, arachidonic acid being the most potent inhibitor, followed by linoleic acid (only tested on spleen microsomes) and oleic acid. By contrast, 1,2-diolein and phosphatidylcholine (dipalmitoyl) showed no or little effect. These results indicate that glandular gastric mucosa can produce PAF through the 'de novo' pathway, and that fatty acids, especially unsaturated, can reduce that synthesis by modulating the expression of DTT-insensitive cholinephosphotransferase.


Managing Chemotherapy Extravasation Across Transitions of Care: A Clinical Nurse Specialist Initiative.
Chemotherapy extravasation can lead to serious patient harm in patients with cancer. For nurses who administer vesicant chemotherapy, extravasation is a primary concern. Regardless of nurse experience level and despite prevention strategies, extravasations occur. Literature related to nurse management of chemotherapy extravasation beyond initial treatment is lacking, and no descriptors are available for a formalized process. Communication gaps and a lack of standardized follow-up within a 1400-bed, quaternary care academic medical institution contributes to challenges in care continuity when patients transition between hospital and ambulatory settings. With chemotherapy extravasation, the site does not immediately exhibit signs of tissue injury, leading to a false sense of security. As a result, tissue damage can be significant by the time the patient returns for his or her regular appointment. Two oncology clinical nurse specialists (CNSs) recognized an opportunity to bridge the gap and overcome the challenges by addressing patient needs postextravasation. Between 2015 and 2016, a formal consult process was designed, approved, and implemented to observe, manage, and make recommendations for timely care and follow-up. Since implementation of the process, the oncology CNSs have received multiple requests for consultations. Nursing staff report increased comfort levels with this process in place. A formalized process for managing chemotherapy extravasations increases patient safety and patient and nurse satisfaction.


The bioactivity of composite Fmoc-RGDS-collagen gels.
The incorporation of small bioactive peptide motifs within robust hydrogels constitutes a facile procedure to chemically functionalise cell and tissue scaffolds. In this study, a novel approach to utilise Fmoc-linked peptide amphiphiles comprising the bio-functional cell-adhesion RGDS motif within biomimetic collagen gels was developed. The composite scaffolds thus created were shown to maintain the mechanical properties of the collagen gel while presenting additional bio-activity. In particular, these materials enhanced the adhesion and proliferation of viable human corneal stromal fibroblasts by 300% compared to non-functionalised gels. Furthermore, the incorporation of Fmoc-RGDS nanostructures within the collagen matrix significantly suppressed gel shrinkage resulting from the contractile action of encapsulated fibroblasts once activated by serum proteins. These mechanical and biological properties demonstrate that the incorporation of peptide amphiphiles provides a suitable and easy method to circumvent specific biomaterial limitations, such as cell-derived shrinkage, for improved performance in tissue engineering and regenerative medicine applications.


Time and stimulus specificity in extinction of the conditioned nictitating membrane response in the rabbit (Oryctolagus cuniculus).
The present experiments demonstrated that, in the rabbit nictitating membrane preparation, a conditioned response (CR) can be selectively eliminated in one portion of a conditioned stimulus (CS) while it is still paired with the unconditioned stimulus (US). Rabbits were initially trained with two stimuli (tone, light). Each was paired with the US by using a mixture of two CS-US interstimulus intervals (ISIs): 200 ms and 1,200 ms in Experiment 1; 150 ms and 500 ms in Experiment 2. The CRs showed double peaks, one for each ISI. Subsequently, one CS (A) was trained with only the longer ISI, whereas the other CS (B) continued to be trained with both ISIs. Consequently, the CR peak based on the shorter ISI disappeared for CSA but not for CSB. The later CR peaks during both CSA and CSB were maintained. These results support time-based models of conditioning. Implications for proposed mechanisms of extinction are discussed.


Synthesis and pharmacological evaluation of a potent and selective σ1 receptor antagonist with high antiallodynic activity.
Based on the pharmacophore model of Glennon the conformationally restricted σ(1) receptor ligand 2 with a 1,3-dioxane moiety has been designed and synthesized. The three step synthesis (transacetalization with pentane-1,3,5-triol, tosylation, and nucleophilic substitution with benzylamine) provided diastereoselectively the cis-configured 1,3-dioxane 2 in good yields. The 1,3-dioxane 2 represents a potent σ(1) receptor ligand (K(i) = 19 nM) with moderate selectivity over the σ(2) subtype (K(i) = 92 nM) and excellent selectivity against more than 60 other targets. Additionally the hERG K(+) channel is not affected by 2. In the capsaicin assay 2 showed extraordinarily high analgesic activity with more than 70% analgesia at the very low dose of 0.25 mg/kg body weight, which indicates σ(1) antagonistic activity. Since 2 does only interact with σ(1) receptors, the in-vivo antiallodynic activity of 2 must be attributed to the σ(1) antagonistic activity.


Elimination of preexistent acetylcholine receptor clusters induced by the formation of new clusters in the absence of nerve.
Acetylcholine receptors (AChRs) form clusters spontaneously in cultured Xenopus myotomal muscle cells in the absence of innervation. Innervation causes a dispersal of these clusters, as well as the formation of new clusters along the neuromuscular contact. To examine whether this dispersal process is dependent upon the presence of the nerve or can be effected by the formation of new clusters alone, we examined the stability of the preexistent clusters during the formation of new AChR clusters induced by basic polypeptide-coated latex beads. These beads cause a rapid development of clusters in cultured Xenopus muscle cells, and the size and the number of clusters can be experimentally manipulated by varying the size and number of beads applied to the culture. Accompanying the bead-induced formation of new clusters was an observed suppression of preexistent clusters, as shown by fluorescence microscopy after staining with rhodamine-conjugated alpha-bungarotoxin. This process of extra-bead cluster removal can be speeded up by treating the cultures with more beads or using beads of larger diameter. Furthermore, if the beads are applied before the spontaneous AChR clustering, no extra-bead clusters are formed. Thus, the latex beads can mimic the nerve in both causing the formation of new clusters and the dispersal of preexistent clusters. Although the receptor clusters are dispersed by the beads, the density of diffuse receptors, as shown by autoradiography with 125I-conjugated alpha-bungarotoxin does not decrease in the short-term cultures under study. This indicates that the dispersal of preexistent clusters is not due to a depletion of the surface pool of AChRs.(ABSTRACT TRUNCATED AT 250 WORDS)


[Acute mixed-cell human leukemia].
The incidence rate of acute mixed-lineal leukemias, distinguished in a group of patients with acute non-lymphoblastic leukemia, in children and adults was about the same: CALLA 10-20%, T-cell antigens 15-22%, Thy-1 15-17%. The incidence rate of acute lymphoblastic leukemia with myeloid (17-21%) and erythroid (12-13%) antigens did not significantly differ in children and adults. Distinguishing features have been proposed for actual acute mixed-lineal leukemias having markers of mature stages of varying cell line differentiation from cryptic lineal-different-marker leukemias of bi- or polypotent precursor-cell origin.


[Gallstones in children. Report of one case and review of the literature (author's transl)].
A 12 year old boy is presented with choleithiasis and cholecystitis diagnosed by oral cholecistogram and intravenous cholangiogram and managed surgically with a cholecystectomy. A review of 667 cases of cholelithiasis in children is presented from literature, since the first report of gallstones in 1737, until 1975. It is showed that childhood cholelithiasis is a uncommon disease, occurring in all ages but (commoner) in preadolescent and adolescent girls. Etiologic significance of obesity, family history of cholelithiasis, pregnancy and history of previous abdominal surgery is reported. Haemolytic disease is an underlying etiologic agent in less than 19% of 416 cases reviewed. A high percentage of gallstones were visible on plain films of the abdomen and oral cholecystograms were diagnostic of cholelithiasis or showed changes highly suggestive of gallstones in 86% of cases reviewed. In a child with abdominal pain of unknown etiology, it is imperative to exculade the possibility of gallstones, and plain films of the abdomen and oral cholecystography are the best investigative techniques to do this.


Characterization of a tricationic trigonal bipyramidal iron(IV) cyanide complex, with a very high reduction potential, and its iron(II) and iron(III) congeners.
Currently, there are only a handful of synthetic S = 2 oxoiron(IV) complexes. These serve as models for the high-spin (S = 2) oxoiron(IV) species that have been postulated, and confirmed in several cases, as key intermediates in the catalytic cycles of a variety of nonheme oxygen activating enzymes. The trigonal bipyramidal complex [Fe(IV)(O)(TMG(3)tren)](2+) (1) was both the first S = 2 oxoiron(IV) model complex to be generated in high yield and the first to be crystallographically characterized. In this study, we demonstrate that the TMG(3)tren ligand is also capable of supporting a tricationic cyanoiron(IV) unit, [Fe(IV)(CN)(TMG(3)tren)](3+) (4). This complex was generated by electrolytic oxidation of the high-spin (S = 2) iron(II) complex [Fe(II)(CN)(TMG(3)tren)](+) (2), via the S = 5/2 complex [Fe(III)(CN)(TMG(3)tren)](2+) (3), the progress of which was conveniently monitored by using UV-vis spectroscopy to follow the growth of bathochromically shifting ligand-to-metal charge transfer (LMCT) bands. A combination of X-ray absorption spectroscopy (XAS), Mössbauer and NMR spectroscopies was used to establish that 4 has a S = 0 iron(IV) center. Consistent with its diamagnetic iron(IV) ground state, extended X-ray absorption fine structure (EXAFS) analysis of 4 indicated a significant contraction of the iron-donor atom bond lengths, relative to those of the crystallographically characterized complexes 2 and 3. Notably, 4 has an Fe(IV/III) reduction potential of ∼1.4 V vs Fc(+/o), the highest value yet observed for a monoiron complex. The relatively high stability of 4 (t(1/2) in CD(3)CN solution containing 0.1 M KPF(6) at 25 °C ≈ 15 min), as reflected by its high-yield accumulation via slow bulk electrolysis and amenability to (13)C NMR at -40 °C, highlights the ability of the sterically protecting, highly basic peralkylguanidyl donors of the TMG(3)tren ligand to support highly charged high-valent complexes.


Exploration of the Factors Affecting the Choices of Nursing Students Who Choose Psychiatric Nursing as the First and Last Choice.
The aim of this qualitative study was to explore the factors that affect the choices of nursing students who chose a psychiatric nursing internship. The sample group of the study consisted of 13 students who listed psychiatric nursing as their first choice and 11 students who listed psychiatric nursing as their last choice. Four themes were determined: personal reasons, stigmatization, experiences related to psychiatric nursing, and perception of care. Providing activities in nursing education to reduce stigmatization and increasing the time allocated for psychiatric nursing theory and practice are recommended.


[Microalgae Spirulina in human nutrition].
Spirulina microalgae (Spirulina platensis, Spirulina maxima, Spirulina fusiformis) is considered as a valuable additional food source of some macro- and micronutrients including high quality protein, iron, gamma-linolenic fatty acid, carotenoids, vitamins B1 and B2. In spite of Spirulina chemical composition varies widely when grown in open reservoirs its efficiency as an additional remedy in treatment and prophylaxis of different diseases is proved in a variety of experimental and clinical trials. During Spirulina cultivation in open reservoirs and especially in closed photobioreactors its biomass may be additionally enriched with some trace elements such as iron, iodine, selenium, zinc, copper, manganese and chromium in high bioavailable form. Said biomass is considered as a constituent of new bioactive food supplements.


[Synchrotron radiation techniques for structural characterisation of biological entities: an example with renal stone analysis].
This paper describes the opportunities given by the synchrotron radiation techniques regarding the structural characterisation of biological entities. After a short recall on the characteristics of the synchrotron radiation, are described the experimental devices based on fluorescence X, wide angle X-ray scattering and X-ray absorption spectroscopy, which may applied for biological samples, especially in the field of stone analysis. Recent progresses in medical research using synchrotron radiation will be also discussed.


Is migraine a genetic illness? The various forms of migraine share a common genetic cause.
Is migraine a genetic illness? This question was previously controversial, but today the answer yes is generally accepted. The scientific evidence is the significantly increased familial risk of migraine, and the significantly higher concordance rate of migraine in monozygotic than dizygotic twin pairs. Finally, the three identified ion-channel genes that can cause familial hemiplegic migraine provide very strong evidence of genetics. Mutations in these genes can also cause sporadic hemiplegic migraine. The next question is whether the different types of migraine, i.e. migraine without aura, migraine with aura, sporadic hemiplegic migraine and familial hemiplegic migraine share a common genetic cause. This question is at present controversial. However, the fact that all types of migraine are paroxystic in nature suggest that a common genetic cause could be mutations in ion channels, although a common mutation has not yet been identified in the more common types of migraine: migraine without aura and migraine with aura.


Video fluorescence microscopy studies of phospholipid vesicle fusion with a planar phospholipid membrane. Nature of membrane-membrane interactions and detection of release of contents.
Video fluorescence microscopy was used to study adsorption and fusion of unilamellar phospholipid vesicles to solvent-free planar bilayer membranes. Large unilamellar vesicles (2-10 microns diam) were loaded with 200 mM of the membrane-impermeant fluorescent dye calcein. Vesicles were ejected from a pipette brought to within 10 microns of the planar membrane, thereby minimizing background fluorescence and diffusion times through the unstirred layer. Vesicle binding to the planar membrane reached a maximum at 20 mM calcium. The vesicles fused when they were osmotically swollen by dissipating a KCl gradient across the vesicular membrane with the channel-forming antibiotic nystatin or, alternatively, by making the cis compartment hyperosmotic. Osmotically induced ruptures appeared as bright flashes of light that lasted several video fields (each 1/60 s). Flashes of light, and therefore swelling, occurred only when channels were present in the vesicular membrane. The flashes were observed when nystatin was added to the cis compartment but not when added to the trans. This demonstrates that the vesicular and planar membranes remain individual bilayers in the region of contact, rather than melding into a single bilayer. Measurements of flash duration in the presence of cobalt (a quencher of calcein fluorescence) were used to determine the side of the planar membrane to which dye was released. In the presence of 20 mM calcium, 50% of the vesicle ruptures were found to result in fusion with the planar membrane. In 100 mM calcium, nearly 70% of the vesicle ruptures resulted in fusion. The methods of this study can be used to increase significantly the efficiency of reconstitution of channels into planar membranes by fusion techniques.


Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients.
Gastrointestinal stromal tumors (GISTs) represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) or platelet derived growth factor receptor α (PDGFRA) genes. However, whether genotype analysis should be regarded as a prognostic indicator remains unclear. In the present study, clinicopathological data and the mutation phenotypes of KIT and PDGFRA genes were assessed in a series of 302 patients with GISTs at a single center. Univariate and multivariate Cox regression analyses were performed to identify the clinicopathological and mutational factors associated with relapse-free survival (RFS) in patients who had undergone complete primary GIST resection. KIT and PDGFRA mutations were identified in 233 (77.2%) and 30 (9.9%) cases, respectively. The following clinicopathological parameters were significantly associated with a shorter RFS: Male, non-gastric tumor origin, larger tumor size (>5 cm), high mitotic activity (>5/50 high-power fields), necrosis and epithelioid morphology. Tumors at non-gastric sites, with high National Institutes of Health risk classification, high World Health Organization (WHO) grade and KIT deletion involving codons 557/558/559 exhibited a significantly higher risk of progression. In the Cox regression model, KIT deletion involving codons 557/558/559, non-gastric origin and high WHO grade were independent indicators of RFS. The adverse prognosis associated with KIT deletions involving codons 557/558/559 was also observed for gastric GISTs. Conversely, spindle morphology, KIT exon 11 substitution and PDGFRA exon 18 mutation were associated with a longer RFS and lower rate of relapse. Furthermore, the coexistence of KIT exon 11 deletion and exon 13 duplication was observed in one tumor, with adverse prognostic features. Heterogeneity affecting morphology, immunostaining and genotype was identified in 4 cases. In addition, the presence of succinate dehydrogenase-deficient GIST was found in 5 cases (3.6%). In conclusion, the tumor genotype with regard to KIT and PDGFRA mutations exhibited prognostic significance for the risk of GIST progression and may be helpful for the optimization of tailored adjuvant therapy.


Antiperistaltic ileal segment in the prevention of ileostomy diarrhea.
Diarrhea, often profuse, accompanied by skin excoriation and nutritional and electrolyte depletion is a major complication of ileostomy. In an attempt to improve the course of these patients, an experimental study using dogs was undertaken to investigate an antiperistaltic ileal segment for the prevention of ileostomy diarrhea. Ileostomies were created in dogs. All the dogs with ileostomies died within nine days of weight loss and massive electrolyte and water depletion. A second group of animals underwent creation of an ileostomy simultaneously, with an antiperistaltic ileal segment placed 30.5 cm proximal to the ileostomy. These dogs maintained their weight and electrolyte and water balance. The stools in the group with the reversed ileal segment became semisolid to solid, compared to the watery diarrhea of dogs with ileostomies only.


The K = 2 conundrum.
Assessments of population genetic structure have become an increasing focus as they can provide valuable insight into patterns of migration and gene flow. structure, the most highly cited of several clustering-based methods, was developed to provide robust estimates without the need for populations to be determined a priori. structure introduces the problem of selecting the optimal number of clusters, and as a result, the ΔK method was proposed to assist in the identification of the "true" number of clusters. In our review of 1,264 studies using structure to explore population subdivision, studies that used ΔK were more likely to identify K = 2 (54%, 443/822) than studies that did not use ΔK (21%, 82/386). A troubling finding was that very few studies performed the hierarchical analysis recommended by the authors of both ΔK and structure to fully explore population subdivision. Furthermore, extensions of earlier simulations indicate that, with a representative number of markers, ΔK frequently identifies K = 2 as the top level of hierarchical structure, even when more subpopulations are present. This review suggests that many studies may have been over- or underestimating population genetic structure; both scenarios have serious consequences, particularly with respect to conservation and management. We recommend publication standards for population structure results so that readers can assess the implications of the results given their own understanding of the species biology.


[Cytochemical study of various stages of the life cycle of Toxoplasma gondii. 3. Phosphatases in the entozoa].
Three methods were used to detect acid phosphatase in toxoplasma endodozoites of strain SS-119 harvested on day 4 after mouse inoculation. The modified lead nitrate method detected the enzymatic activity in host cells only; Gomori metal salt technique revealed the enzyme almost exclusively in the parasite, whereas the Standard Naphthol AS-BI phosphate method suggested the presence of the enzyme simultaneously in the two, though not regularly in the parasites. The enzymatic activity when present was visualized as few coloured granules mainly in the anterior cytoplasmic area on the body and at the periphery, leaving the nuclear zone unstained. Alkaline phosphatase distribution, detected with one method only (Standard Naphtol AS-BI phosphate), appeared less convincing in the parasite than in the host cell. In host cells harbouring endozoites, no increased activity was observed in the immediate closeness of the intracellular parasites.


Deer antlers: the fastest growing tissue with least cancer occurrence.
Deer antlers are a bony organ solely able to acquired distinct unique attributes during evolution and all these attributes are against thus far known natural rules. One of them is as the fastest animal growing tissue (2 cm/day), they are remarkably cancer-free, despite high cell division rate. Although tumor-like nodules on the long-lived castrate antlers in some deer species do occur, but they are truly benign in nature. In this review, we tried to find the answer to this seemingly contradictory phenomenon based on the currently available information and give insights into possible clinic application. The antler growth center is located in its tip; the most intensive dividing cells are resident in the inner layer of reserve mesenchyme (RM), and these cells are more adopted to osteosarcoma rather than to normal bone tissues in gene expression profiles but acquire their energy mainly through aerobic oxidative phosphorylation pathway. To counteract propensity of neoplastic transformation, antlers evolved highly efficient apoptosis exactly in the RM, unparalleled by any known tissues; and annual wholesale cast to jettison the corps. Besides, some strong cancer suppressive genes including p53 cofactor genes and p53 regulator genes are highly positively selected by deer, which would have certainly contributed to curb tumorigenesis. Thus far, antler extracts and RM cells/exosomes have been tried on different cancer models either in vitro or in vivo, and all achieved positive results. These positive experimental results together with the anecdotal folklore that regular consumption of velvet antler is living with cancer-free would encourage us to test antlers in clinic settings.


Estimating axon radius using diffusion-relaxation MRI: calibrating a surface-based relaxation model with histology.
Axon radius is a potential biomarker for brain diseases and a crucial tissue microstructure parameter that determines the speed of action potentials. Diffusion MRI (dMRI) allows non-invasive estimation of axon radius, but accurately estimating the radius of axons in the human brain is challenging. Most axons in the brain have a radius below one micrometer, which falls below the sensitivity limit of dMRI signals even when using the most advanced human MRI scanners. Therefore, new MRI methods that are sensitive to small axon radii are needed. In this proof-of-concept investigation, we examine whether a surface-based axonal relaxation process could mediate a relationship between intra-axonal T2 and T1 times and inner axon radius, as measured using postmortem histology. A unique in vivo human diffusion-T1-T2 relaxation dataset was acquired on a 3T MRI scanner with ultra-strong diffusion gradients, using a strong diffusion-weighting (i.e., b = 6,000 s/mm2) and multiple inversion and echo times. A second reduced diffusion-T2 dataset was collected at various echo times to evaluate the model further. The intra-axonal relaxation times were estimated by fitting a diffusion-relaxation model to the orientation-averaged spherical mean signals. Our analysis revealed that the proposed surface-based relaxation model effectively explains the relationship between the estimated relaxation times and the histological axon radius measured in various corpus callosum regions. Using these histological values, we developed a novel calibration approach to predict axon radius in other areas of the corpus callosum. Notably, the predicted radii and those determined from histological measurements were in close agreement.


Phase II study of R-CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study.
The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation. Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.


Identification of patients at high risk for death and cardiac ischemic events after hospital discharge.
Patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) remain at risk for death and cardiac ischemic events after being discharged from the hospital. We examined whether the Thrombolysis In Myocardial Infarction (TIMI) risk score for UA/NSTEMI, ascertained at presentation in patients enrolled in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI (ESSENCE) trials, could be used to identify patients at high risk for major cardiac events after hospital discharge. There were a total of 1218 major cardiac events, defined as death, nonfatal myocardial infarction, or urgent revascularization, by day 43. Of these events, 336 (28%) occurred in patients after they were discharged from the hospital. Use of the TIMI risk score for UA/NSTEMI revealed a progressive, statistically significant increase in the rate of events after leaving the hospital as the patients' baseline level of risk increased (P <.001 for chi(2) test for trend). For patients with a risk score of 5 to 7, treatment with enoxaparin during the acute phase was associated with an odds ratio of 0.51 (95% CI 0.29-0.91) for the occurrence of death and cardiac ischemic events after hospital discharge. More than one fourth of the major cardiac events that will occur in the first 6 weeks occur after discharge from the hospital. Stratification at presentation on the basis of the TIMI risk score for UA/NSTEMI can be used to identify patients at high risk for these events. Among patients at high-risk, acute-phase treatment with enoxaparin significantly reduces the risk of major cardiac events after leaving the hospital.


Solid-phase microextraction of 2,4,6-trinitrotoluene using a molecularly imprinted-based fiber.
A molecularly imprinted polymer with trinitrotoluene as the template molecule was synthesized and used as the novel coating for solid-phase microextraction of the nitroaromatic explosive 2,4,6-trinitrotoluene for its selective determination. The fiber was characterized in terms of coating thickness, morphology, intra- and inter-batch repeatability and extraction efficiency. An average thickness of 50 ± 4 μm with a uniform distribution of the coating was obtained. Good performances of the developed procedure in term of both intra-batch and inter-batch repeatability with relative standard deviations <8% were obtained. Finally, detection and quantitation limits in the low nanogram per kilogram levels were achieved proving the superior extraction capability of the developed coating, obtaining gas chromatography-mass spectrometry responses about two times higher than those achieved using commercial devices.


Zinc supplementation for pediatric pneumonia.
Question Among young children suffering from pneumonia, zinc deficiency has been documented in many countries. Is supplementation with zinc effective in the treatment and prevention of childhood pneumonia? Answer Several studies reported that zinc supplementation for more than 3 months was effective for preventing pneumonia in children younger than 5 years of age; however, the evidence is not sufficient to confirm its prophylactic properties if it is given for shorter periods of time. Adjunctive zinc supplementation for treatment of pneumonia has failed to show a benefit.


De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes.
KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the BK current, whereas p.(Cys413Tyr) and p.(Pro805Leu) reduced the BK current amplitude and shifted the activation curves toward positive potentials. The p.(Asp984Asn) variant reduced the current amplitude without affecting kinetics. A phenotypic analysis of the patients carrying the recurrent p.(Gly375Arg) de novo missense LoF variant revealed a novel syndromic neurodevelopmental disorder associated with severe developmental delay, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic dysmorphic features. Patients with other LoF variants presented with neurological and developmental symptoms including developmental delay, intellectual disability, ataxia, axial hypotonia, cerebral atrophy and speech delay/apraxia/dysarthria. Therefore, LoF KCNMA1 variants are associated with a new syndrome characterized by a broad spectrum of neurological phenotypes and developmental disorders. LoF variants of KCNMA1 cause a new syndrome distinctly different from gain-of-function variants in the same gene.


Survey and Synthesis of State of the Art in Driver Monitoring.
Road vehicle accidents are mostly due to human errors, and many such accidents could be avoided by continuously monitoring the driver. Driver monitoring (DM) is a topic of growing interest in the automotive industry, and it will remain relevant for all vehicles that are not fully autonomous, and thus for decades for the average vehicle owner. The present paper focuses on the first step of DM, which consists of characterizing the state of the driver. Since DM will be increasingly linked to driving automation (DA), this paper presents a clear view of the role of DM at each of the six SAE levels of DA. This paper surveys the state of the art of DM, and then synthesizes it, providing a unique, structured, polychotomous view of the many characterization techniques of DM. Informed by the survey, the paper characterizes the driver state along the five main dimensions-called here "(sub)states"-of drowsiness, mental workload, distraction, emotions, and under the influence. The polychotomous view of DM is presented through a pair of interlocked tables that relate these states to their indicators (e.g., the eye-blink rate) and the sensors that can access each of these indicators (e.g., a camera). The tables factor in not only the effects linked directly to the driver, but also those linked to the (driven) vehicle and the (driving) environment. They show, at a glance, to concerned researchers, equipment providers, and vehicle manufacturers (1) most of the options they have to implement various forms of advanced DM systems, and (2) fruitful areas for further research and innovation.


Dosimetry in radionuclide therapies with 90Y-conjugates: the IEO experience.
The basis for a successful radionuclide therapy is a high and stable uptake of the radiopharmaceutical in the target tissue along with low activity concentration in other normal organs. The contribution of dosimetry in radionuclide therapy is to predict before the treatment the absorbed doses in tumor and normal organs, to identify the critical organs, to minimize any possible toxicity and to evaluate the maximum tolerated dose. We report our experience concerning pharmacokinetics and dosimetry of two 90Y-therapeutic protocols: 3-step pretargeting radioimmunotherapy (RIT) according to the biotin-avidin system and receptor mediated radionuclide therapy with the somatostatin analogue [DOTA-D-Phe1-Tyr3] octreotide named DOTATOC. For the dosimetric analysis, analogous approaches for the two radiolabeled compounds due to the similar pharmacokinetic characteristics were adopted; the MIRD formalism was applied, taking into account both the physical and the biological characteristics of the radioconjugate and patients' metabolism. In order to determine biological clearance, serial blood samples and complete urine collection were obtained up to 48 hours after injection; to evaluate biodistribution, several whole body scans were acquired. Both therapies showed the advantageous characteristics of a fast blood clearance and a predominantly renal excretion of the radiopharmaceuticals thus lowering the irradiation of the total body. Although pharmacokinetic characteristis were similar, different critical organs were found for the two therapies; in particular, some considerations regarding red marrow, spleen and kidneys were required. The results of our studies indicate that high activities of 90Y-biotin (3-step RIT) and 90Y-DOTATOC can be administered with acceptable radiation doses to normal organs.


Indoor metallic pollution and children exposure in a mining city.
Mining industries are known for causing strong environmental contamination. In most developing countries, the management of mining wastes is not adequate, usually contaminating soil, water and air. This situation is a source of concern for human settlements located near mining centers, especially for vulnerable populations such as children. The aim of this study was to assess the correlations of the metallic concentrations between household dust and children hair, comparing these associations in two different contamination contexts: a mining district and a suburban non-mining area. We collected 113 hair samples from children between 7 and 12 years of age in elementary schools in the mining city of Oruro, Bolivia. We collected 97 indoor dust samples from their households, as well as information about the children's behavior. Analyses of hair and dust samples were conducted to measure As, Cd, Pb, Sb, Sn, Cu and Zn contents. In the mining district, there were significant correlations between non-essential metallic elements (As, Cd, Pb, Sb and Sn) in dust and hair, but not for essential elements (Cu and Zn), which remained after adjusting for children habits. Children who played with dirt had higher dust-hair correlations for Pb, Sb, and Cu (P=0.006; 0.022 and 0.001 respectively) and children who put hands or toys in their mouths had higher dust-hair correlations of Cd (P=0.011). On the contrary, in the suburban area, no significant correlations were found between metallic elements in dust and children hair and neither children behavior nor gender modified this lack of associations. Our results suggest that, in a context of high metallic contamination, indoor dust becomes an important exposure pathway for children, modulated by their playing behavior.


Effect of fertiliser on functional properties of flour from four rice varieties grown in Sri Lanka.
Fertiliser is an essential agro-chemical input in modern rice farming. Fertiliser affects the grain quality and yield of rice. Although much research has been carried out to investigate the influence of fertiliser (recommended NPK addition) on yield and quality of rice grain, little is known about the effect of fertiliser on thermal, pasting, gelling and retrogradation properties of rice flour. The aim of this study was to investigate the influence of recommended fertilisation on functional properties of rice flour from four popular high yielding rice varieties grown in Sri Lanka. Fertiliser (recommended NPK addition) increased the protein content but reduced the apparent amylose content in rice flour except in BG 357. Swelling power and amylose leaching were decreased by fertilizer. [corrected] Pasting onset temperature, cold paste viscosity and setback were increased but peak viscosity and granular breakdown decreased. In response to the fertiliser application, gelatinisation peak temperature was reduced in all varieties except BG 300. However, compared to pasting properties, gelatinisation parameters were not much affected by fertilisation. The extent of amylopectin retrogradation was decreased by fertiliser in BG 305 and BG 352 but unchanged in the other two varieties. Except in BG 305, fertiliser reduced the gel hardness of rice flour but increased the gel cohesiveness. It is apparent that the increased protein and reduced amylose content caused by fertiliser affect the functional properties of rice flour.


Information filtering in sparse online systems: recommendation via semi-local diffusion.
With the rapid growth of the Internet and overwhelming amount of information and choices that people are confronted with, recommender systems have been developed to effectively support users' decision-making process in the online systems. However, many recommendation algorithms suffer from the data sparsity problem, i.e. the user-object bipartite networks are so sparse that algorithms cannot accurately recommend objects for users. This data sparsity problem makes many well-known recommendation algorithms perform poorly. To solve the problem, we propose a recommendation algorithm based on the semi-local diffusion process on the user-object bipartite network. The simulation results on two sparse datasets, Amazon and Bookcross, show that our method significantly outperforms the state-of-the-art methods especially for those small-degree users. Two personalized semi-local diffusion methods are proposed which further improve the recommendation accuracy. Finally, our work indicates that sparse online systems are essentially different from the dense online systems, so it is necessary to reexamine former algorithms and conclusions based on dense data in sparse systems.


Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.
Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study.


Two-year follow-up of a randomised trial with repeated antenatal betamethasone.
Weekly repeated antenatal corticosteroid treatment improves respiratory outcome but decreases fetal growth and may impair neurodevelopmental outcome. We have previously reported that a single repeat betamethasone (BM) dose neither decreased fetal growth nor improved the outcome of preterm infants during the first hospitalisation. To study prospectively whether a single repeat dose of BM influences neurodevelopment and growth within 2 years. Women with imminent delivery before 34.0 gestational weeks were eligible if they remained undelivered for >7 days after a single course of antenatal BM. After stratification, a single repeat dose of BM (12 mg) or placebo was given. The children underwent neurological and psychometric examinations and a speech evaluation at a corrected age of 2 years. Prospective, blinded evaluation following the randomised multicentre trial. 259 (82%) surviving infants completed the 2-year follow-up, 120 in the BM group and 139 in the placebo group. The rate of survival without severe neurodevelopmental impairment was similar in both groups (BM 98%, placebo 99%). The risk of cerebral palsy (BM 2%, placebo 1%), growth or re-hospitalisation rates (BM 60%, placebo 50%) did not differ between the groups. A single repeat dose of antenatal BM tended not to influence physical growth or neurodevelopment at 2 years of age.


Mediterranean macrothrombocytopenia.
Platelet count, platelet size, and circulating platelet biomass concentration estimates made with an erythrocyte-calibrated electronic sizing system on EDTA-anticoagulated blood samples gave population medians and 95% ranges for 145 asymptomatic Mediterranean and 200 healthy Northern European subjects. The Mediterraneans had lower platelet counts [161,000 (89,000-290,000)/mul compared with 219,000 (148,000-323,000)/mul] and higher arithmetic mean volumes [17.8 (10.8-29.2) cu mum compared with 12.4 (9.9-15.6) cu mum], while the individual lognormal platelet size distribution profiles were comparable [geomatric standard deviations of 1.78 (1.60-1.98) against 1.70 (1.54-1.88)]; and the platelet biomass concentrations, given by count per microliter times mean volume times 10- minus 7 and expressed as a volumetric percentage of whole blood, were almost identical [0.286% (0.216%-0.379%) against 0.272% (0.201%-0.367%)]. Mediterranean macrothrombocytopenia is, therefore, considered a benign morphologic variant that requires differentiation from thrombocytopenias in which the circulating platelet biomass concentration is decreased.


Children's response to terrorism: a critical review of the literature.
The advent of major terrorist assaults has ushered in a sense of insecurity and vulnerability heretofore unknown in the US. There is information about the impact of disasters and trauma on children, but relatively little data on the effects of terrorism. The events of September 11, 2001 have underscored the need to examine this issue. This report summarizes recent studies that address the impact of terrorist incidents on children, and examines issues related to mental health services for children in the post-attack environment. Work related to the 1993 bombing of the World Trade Center, the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City, the 1998 bombing of the American Embassy in Nairobi, Kenya, and the September 11 attacks are reviewed. This article indicates significant challenges in the identification, evaluation, and treatment of children potentially in need of attention.


Program of palliative cancer care--our experience.
Annually more than 27,000 persons die of cancer in the Czech Republic and the overall incidence of malignancies is still increasing. These data shows the need for affordable and good follow-up care especially for patients without any cancer treatment due to irreversible progression of tumor. Currently the outpatient palliative cancer care gets more into the forefront. Prerequisite for a well working outpatient palliative care is cooperation with general practitioners and home health care agencies. The purpose of the so called program of palliative cancer care is to guide a patient in palliative cancer care and to improve the cooperation among health care providers. During the period from January 2008 to October 2010 we evaluated in patient without any oncology treatment due to irreversible progression of tumor. In palliative outpatient clinic we treated 446 patients, 119 of them received home care services with average length of 27.8 days. 77 patients died at home, 51 in health facilities and 41 in inpatient hospice care. We present pilot study focusing on outpatient palliative cancer care which shows the real benefit from early indication of palliative cancer care. This type of care allows patients to stay as long as possible at home among their close relatives.


Critical limb ischaemia in a diabetic population from an Asian Centre: angiographic pattern of disease and 3-year limb salvage rate with percutaneous angioplasty as first line of treatment.
Lower extremity amputation prevention (LEAP) is an ongoing program in our institution aimed at salvaging limbs in patients with critical limb ischemia (CLI). Patients in the LEAP program with reconstructible anatomy on initial Doppler imaging received either bypass surgery or percutaneous transluminal balloon angioplasty (PTA). We present the 3 year limb salvage rate and angiographic disease patterns in 42 consecutive diabetic patients with CLI who received PTA in 2005. 26 women and 16 men with diabetes between the ages of 45 and 91 years old (mean age, 70.8 years) received PTA in 2005. Presenting symptoms were rest pain (n = 22), pre-existing gangrene (n = 17), non-healing ulcer (n = 16) and cellulitis (n = 2). The aim of the PTA was to achieve straight-line flow from the abdominal aorta down to the patent dorsalis pedis or plantar arch, with limb salvage as the ultimate outcome. Failure of treatment was defined as any amputation above the level of a Syme's amputation or the need for further surgical bypass. Technical success was achieved in 90% (38 out of 42 patients). Limb salvage rates were 93% at 1 month, 87% at 3 months, 82% at 6 months, 78% at 1 year, 69% at 2 years and 66% at 3 years. Mortality was 17% (n = 7) at 3 years. Of the 13 patients with failed therapy, 3 underwent bypass, 9 had amputations and 1 had bypass followed by amputation. Four of the cases required further intervention due to worsening gangrene and infection, while the remaining was due to persistent rest pain. The rest of the 32 patients had no lower limb related issues at the end of 3 years, with improvement of the presenting symptoms. Patterns of treated segments were aortoiliac occlusions (n = 3), pure infrapopliteal disease (n = 3), femoropopliteal with at least 1 good infrapopliteal run-off vessel (n = 14) and combined femoropopliteal and infrapopliteal disease (n = 25). Involvement of infrapopliteal vessels that needs to be treated is common in Asian diabetics. While early limb salvage rates up to 1 year are similar, the 3 year limb salvage rates in Asian diabetics are lower than the western population.


Heart rate, blood pressure, and running speed responses to mesencephalic locomotor region stimulation in anesthetized rats.
The decerebrate rat locomotor preparation described in a previous study requires extensive brain surgery with the possibility of significant blood loss. The purpose of this study was to improve on the previous model by using lightly anesthetized instead of decerebrated rats. After initial surgery consisting of boring a small hole through the parietal bone, the animals were maintained on low levels of halothane anesthetic. The mesencephalic locomotor region was then located by physiological criteria using stereotaxic coordinates from the previous study. Locomotor speed, blood pressure and heart rate responses were then measured over a wide range of stimulation currents that elicited a maximal running speed. Stimulation currents ranged from 36 microA for walking to 82 microA for fast galloping. Locomotor speeds ranged from 20 m/min for walking to 64 m/min for fast galloping. Some animals easily achieved galloping speeds beyond 100 m/min. Blood pressure and heart rate increased with increasing stimulation currents. Blood pressure also increased during stimulation after muscular paralysis. This was not due to current spread, suggesting that the mesencephalic locomotor region might be involved in central command mechanisms. Heart rate did not increase after paralysis. This supports other multi-joint dynamic studies suggesting that movement per se may be necessary to induce heart rate changes, presumably via joint mechanoreceptors. The range of locomotor patterns and cardiovascular responses were obtained under self-supported conditions. By defining the mesencephalic locomotor region via physiological criteria, and by grouping blood pressure and heart rate measurements by gait rather than by stimulation currents, the potential use of the intact model for cardiovascular control studies was demonstrated. The animals were able to run and gallop at high speeds considering they were anesthetized. The simplified preparation will be useful for more complex cardiovascular experiments requiring intact and self-supported conditions.


Risk factors in the development of cesarean section infection.
Fifty consecutive patients undergoing cesarean section were evaluated prospectively. A data collection form was developed and 113 variables relating to demographic features, antepartum care, intrapartum events and postpartum course were evaluated. All of the patients were seen and evaluated within 24 hours of delivery and all forms were completed when the patients were discharged from the hospital. Twenty-five of the 50 patients had postpartum febrile morbidity develop. There were 14 instances of endometritis; five, wound infections; two, urinary tract infections; two, upper respiratory tract infections; three pulmonary infections; one patient with phlebitis, and two with febrile morbidity and no apparent source. Factors significantly associated with an increased risk of developing febrile morbidity included antepartum infections, resident staff as primary surgeon, extension of the uterine incision and positive endometrial culture at the time of the operation. Patients undergoing elective repeat cesarean section had less febrile morbidity than others (p less than 0.025). Statistically significant differences between the two groups were not found for the variables obesity, anemia, rupture of membranes, number of pelvic examinations, fetal monitoring, fetal tachycardia, general anesthesia and skin preparation. Operative blood loss was greater in the patients having febrile morbidity develop, but this difference was not statistically significant.


Vasculobiliary complications following adult right lobe split liver transplantation from the perspective of reconstruction techniques.
Split liver transplantation (SLT) compensates for the organ shortage and provides an alternative solution for recipients disadvantaged by a smaller body size. Variations in the hepatic arterial anatomy and reconstructive techniques may lead to more technical complications, and we sought to analyze the incidence and risk factors of vasculobiliary complications with respect to reconstructive techniques. We identified 171 adult right lobe SLT procedures and 1412 whole liver transplantation (WLT) procedures between January 2000 and June 2012 and compared the results of these 2 groups. In the SLT group, arterial reconstruction techniques were classified into 4 subgroups (I-IV), and biliary reconstruction was classified into 2 groups [duct-to-duct (DD) anastomosis and Roux-en-Y hepaticojejunostomy (RH)]. Specific surgical complications were analyzed against reconstruction techniques. The overall incidence of vascular and biliary complications in the SLT group was greater than that in the WLT group (P = 0.009 and P = 0.001, respectively). There was no difference in hepatic artery thrombosis (HAT), but we saw a tendency toward early HAT in the presence of multiple hepatic arteries supplying the right lobe graft (group IV; 20%) in comparison with the other arterial reconstruction groups (P = 0.052). No difference was noticed in the overall incidence of biliary complications in either DD or RH recipients across 4 arterial reconstruction groups. When the arterial reconstruction involved a right hepatic artery (groups II and III) combined with a DD biliary anastomosis, there was a significant preponderance of biliary complications (P = 0.04 and P = 0.01, respectively). There was no survival difference between SLT and WLT grafts. In conclusion, the complications of SLT are directly related to arterial and biliary reconstruction techniques, and this classification helps to identify high-risk reconstructive techniques.


DNase 2 is the main DNA-degrading enzyme of the stratum corneum.
The cornified layer, the stratum corneum, of the epidermis is an efficient barrier to the passage of genetic material, i.e. nucleic acids. It contains enzymes that degrade RNA and DNA which originate from either the living part of the epidermis or from infectious agents of the environment. However, the molecular identities of these nucleases are only incompletely known at present. Here we performed biochemical and genetic experiments to determine the main DNase activity of the stratum corneum. DNA degradation assays and zymographic analyses identified the acid endonucleases L-DNase II, which is derived from serpinB1, and DNase 2 as candidate DNases of the cornified layer of the epidermis. siRNA-mediated knockdown of serpinB1 in human in vitro skin models and the investigation of mice deficient in serpinB1a demonstrated that serpinB1-derived L-DNase II is dispensable for epidermal DNase activity. By contrast, knockdown of DNase 2, also known as DNase 2a, reduced DNase activity in human in vitro skin models. Moreover, the genetic ablation of DNase 2a in the mouse was associated with the lack of acid DNase activity in the stratum corneum in vivo. The degradation of endogenous DNA in the course of cornification of keratinocytes was not impaired by the absence of DNase 2. Taken together, these data identify DNase 2 as the predominant DNase on the mammalian skin surface and indicate that its activity is primarily targeted to exogenous DNA.


Dual-emission fluorescent silicon nanoparticle-based nanothermometer for ratiometric detection of intracellular temperature in living cells.
In this article, we present a kind of dual-emission fluorescent nanothermometer, which is made of europium (Eu3+)-doped silicon nanoparticles (Eu@SiNPs), allowing the detection of intracellular temperature in living cells with high accuracy. In particular, the presented SiNP-based thermometer features dual-emission fluorescence (blue (455 nm) and red (620 nm) emission), negligible toxicity (cell viability of treated cells remains above 90% during 24 h of treatment) and robust photostability in living cells (i.e., preserving >90% of fluorescence intensity after 45 min of continuous UV irradiation). More significantly, the fluorescence intensity of the Eu@SiNPs exhibits a linear ratiometric temperature response in a broad range from 25 to 70 °C. Taking advantage of these attractive merits, the Eu@SiNP-based nanothermometer is able to accurately (∼4.5% change per °C) determine dynamic changes in intracellular temperature in a quantitative and long-term (i.e., 30 min) manner.


Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein.
Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons.


Evidence for a genetic overlap between body dysmorphic concerns and obsessive-compulsive symptoms in an adult female community twin sample.
Body dysmorphic disorder (BDD) is thought to be etiologically related to obsessive-compulsive disorder (OCD) but the available evidence is incomplete. The current study examined the genetic and environmental sources of covariance between body dysmorphic and obsessive-compulsive symptoms in a community sample of adult twins. A total of 2,148 female twins (1,074 pairs) completed valid and reliable measures of body dysmorphic concerns and obsessive-compulsive symptoms. The data were analyzed using bivariate twin modeling methods and the statistical programme Mx. In the best-fitting model, the covariation between body dysmorphic and obsessive-compulsive traits was largely accounted for by genetic influences common to both phenotypes (64%; 95% CI: 0.50-0.80). This genetic overlap was even higher when specific obsessive-compulsive symptom dimensions were considered, with up to 82% of the phenotypic correlation between the obsessing and symmetry/ordering symptom dimensions and dysmorphic concerns being attributable to common genetic factors. Unique environmental factors, although influencing these traits individually, did not substantially contribute to their covariation. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance. The association between body dysmorphic concerns and obsessive-compulsive symptoms is largely explained by shared genetic factors. Environmental risk factors were largely unique to each phenotype. These results support current recommendations to group BDD together with OCD in the same DSM-5 chapter, although comparison with other phenotypes such as somatoform disorders and social phobia is needed.


Historical look at nursing in the field of mental retardation in the United States.
An account of nursing in the field of mental retardation was examined. Educational preparation, professional identity, workday, and salaries were discussed. The influence of attitudes towards persons with mental retardation on this nursing specialization was emphasized.


Pediatric gastroesophageal reflux.
Gastroesophageal reflux occurs in up to 65 percent of healthy infants. The initial differentiation of physiologic reflux with harmless spitting up from pathologic reflux is often difficult to achieve. Gastroesophageal reflux is caused by transient and intermittent lower esophageal sphincter relaxations unrelated to swallowing. Many tests are available for the diagnosis of gastroesophageal reflux, each with specific indications and limitations. Although no one test is always best, 24-hour esophageal pH monitoring remains the "gold standard" for diagnosis. Its major limitations are its inability to detect reflux for up to two hours following feedings because of the neutralizing effect of the feeding, the lack of correlation with clinical gastroesophageal reflux severity, the expense and the invasive nature of the test. Treatment is determined by the specific presentation. Management of physiologic reflux consists of parental reassurance and counseling about feeding and positioning techniques. Approaches to the management of pathologic reflux range from the use of histamine H2-receptor blockers and prokinetic medications to surgery in severe cases.


Leg length discrepancy in total hip arthroplasty: comparison of two methods of measurement.
Measurement of leg length discrepancy is an important part in planning a successful total hip arthroplasty (THA). Many clinical and radiological methods with variable degrees of accuracy have been advocated to carry out this measurement. We studied the accuracy of a commonly used clinical method by comparing it to a well-known and reliable radiological method. A total of 139 patients aged 44-89 (mean: 67.5 years) scheduled to undergo THA were examined for clinical and radiological leg length discrepancy measurements before and after the operation by the same observers. There was a poor correlation between the clinical and radiological methods preoperatively [r = 0.21, intra-class correlation coefficient (ICC) = 0.33]. The correlation was better postoperatively (r = 0.45, ICC = 0.62). The clinical method used is not recommended for leg length discrepancy measurement preoperatively. Caution should even be taken when using this method postoperatively. The authors recommend using the radiological method when measuring leg length discrepancy as a part of planning for THA.


Visual-spatial ability is more important than motivation for novices in surgical simulator training: a preliminary study.
To investigate whether surgical simulation performance and previous video gaming experience would correlate with higher motivation to further train a specific simulator task and whether visual-spatial ability would rank higher in importance to surgical performance than the above. It was also examined whether or not motivation would correlate with a preference to choose a surgical specialty in the future and if simulator training would increase the interest in choosing that same work field. Motivation and general interest in surgery was measured pre- and post-training in 30 medical students at Karolinska Institutet who were tested in a laparoscopic surgical simulator in parallel with measurement of visual-spatial ability and self-estimated video gaming experience. Correlations between simulator performance metrics, visual-spatial ability and motivation were statistically analyzed using regression analysis. A good result in the first simulator trial correlated with higher self-determination index (r =-0.46, p=0.05) in male students. Visual-spatial ability was the most important underlying factor followed by intrinsic motivation score and finally video gaming experience (p=0.02, p=0.05, p=0.11) regarding simulator performance in male students. Simulator training increased interest in surgery when studying all subjects (p=0.01), male subjects (p=0.02) as well as subjects with low video gaming experience (p=0.02). This preliminary study highlights individual differences regarding the effect of simulator training on motivation that can be taken into account when designing simulator training curricula, although the sample size is quite small and findings should be interpreted carefully.


Variation in the genome of rice tungro bacilliform virus: molecular characterization of six isolates.
The DNA genomes of isolates of rice tungro bacilliform virus from Bangladesh, India, Indonesia, Malaysia and Thailand were cloned and compared with that of the type isolate from the Philippines. Restriction endonuclease maps revealed differences between the isolates and cross-hybridization showed that they fell into two groups, those from the Indian subcontinent and those from south-east Asian countries. The genomes of isolates from the Indian subcontinent contained a deletion of 64 bp when compared with those from south-east Asia. The implications of this variation are discussed.


Association between alcohol use and inflammatory biomarkers over time among younger adults with HIV-The Russia ARCH Observational Study.
Biomarkers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]), and altered coagulation (D-dimer) are associated with increased mortality risk in people with HIV. The objective of the Russia Alcohol Research Collaboration on HIV/AIDS (ARCH) study was to evaluate the association between heavy alcohol use and inflammatory biomarkers over time. The study sought antiretroviral therapy naive participants with HIV (n = 350) and assessed them at baseline, 12 and 24 months. Linear mixed effects models were used to determine whether heavy drinking (self-report augmented by phosphatidylethanol [PEth], an alcohol biomarker) was longitudinally associated with IL-6, sCD14 and D-dimer adjusting for potential confounders (e.g., demographics, HIV factors, comorbid conditions). Participants' baseline characteristics were as follows: 71% male; mean age of 34 years; 87% self-reported hepatitis C; and 86% current smokers. Mean log10 (HIV RNA) was 4.3 copies/mL. Heavy alcohol use, based on National Institute of Alcohol Abuse and Alcoholism risky drinking criteria and PEth (versus non-heavy alcohol use) was associated with higher sCD14 (adjusted mean difference 125 ng/mL [95% CI: 42, 209]), IL-6 (ratio of means 1.35 [95% CI: 1.17, 1.55] pg/mL), and D-dimer (ratio of means 1.20 [95% CI: 1.06, 1.37] ug/mL) across the two-year follow-up. Among HIV+ adults, current heavy alcohol use is associated with higher sCD14, IL-6 and D-dimer over time. Since these biomarkers are associated with mortality, interventions to mitigate effects of heavy drinking on these immune processes merit consideration.


Neuropeptide Y inhibits renin release by a pertussis toxin-sensitive mechanism.
The effects of neuropeptide Y (NPY) were studied in the isolated rat kidney, which was perfused at constant perfusion pressure with a synthetic medium. In this preparation NPY produced concentration (1-100 nM)-dependent inhibition of renin release and vasoconstriction. In kidneys perfused at constant flow, inhibition of renin release by NPY was even more pronounced, excluding a flow-dependent washout effect. The simultaneous infusion of the calcium channel antagonist methoxyverapamil (2 microM) or of the calmodulin inhibitor calmidazolium (1 microM) did not prevent these effects of NPY, suggesting that calcium-dependent reactions are not primarily involved. Inhibition of renin release by NPY was also observed in tissue pieces prepared from the hydronephrotic rat kidney, in which tubular elements are lacking. This indicates that inhibition of renin release by NPY is not dependent on the presence of macula densa cells or on changes of intrarenal hemodynamics. In isolated kidneys from rats pretreated with pertussis toxin (2 micrograms/100 g ip) both effects of NPY, renal vasoconstriction and inhibition of renin release, were almost completely abolished. The pertussis toxin-sensitive factor mediating the effects of NPY is most likely the Ni-coupling protein of the adenylate cyclase complex. Accordingly, our data suggest that NPY induces renal vasoconstriction and inhibits renin release by inhibition of adenylate cyclase activity in vascular smooth muscle and renin-producing cells.


The Three-spined Stickleback, Gasterosteus aculeatus Linnaeus 1758, plays a minor role as a host of Lepeophtheirus salmonis (Krøyer 1837) in the Gulf of Maine.
The sea louse, Lepeophtheirus salmonis (Krøyer 1837), is a significant parasite of farmed salmon throughout the Northern Hemisphere. Management of on-farm louse populations can be improved by understanding the role that wild fish play in sustaining and providing refuge for the local population of sea lice. In this study, 1,064 sticklebacks were captured. Of these animals, 176 individuals were carrying a total of 238 sea lice, yielding a prevalence and intensity of 16.5% and 1.4 lice per fish, respectively. Detailed examination of the sea lice on the three-spined sticklebacks captured in Cobscook Bay found two L. salmonis individuals using three-spined sticklebacks as hosts. A 2012 survey of wild fish in Cobscook Bay, Maine, found multiple wild hosts for Caligus elongatus (von Nordmann 1832), including three-spined sticklebacks (Gasterosteus aculeatus L.), but no L. salmonis were found in this earlier study.


von Willebrand factor antagonizes nitric oxide synthase to promote insulin resistance during hypoxia.
Hypoxic respiratory diseases or hypoxia exposures are frequently accompanied by glucose intolerance and impaired nitric oxide (NO) availability. However, the molecular mechanism responsible for impaired NO production and insulin resistance (IR) during hypoxia remains obscure. In this study, we investigated the possible mechanism of impaired NO production and IR during hypoxia in a mouse model. Mice were exposed to hypoxia for different periods of time (0-24 h), and parameters of IR and endothelial dysfunctions were analyzed. Exposure to hypoxia resulted in a time-dependent increase in IR as well as multimeric forms of von Willebrand factor (vWF) and subsequently a decrease in eNOS activity. Preincubation with plasma of hypoxia-exposed animals (different time points) or human vWF inhibited insulin-induced NO production in a dose-dependent manner; larger doses of insulin reversed the effect. In contrast, preincubation of vWF-immunodepleted plasma failed to inhibit insulin-induced NO production, whereas vWF immunoneutralization abolished the effect of hypoxia-induced IR and D-[U-(14)C]glucose uptake. Furthermore, the interactions between vWF and eNOS were studied by far-Western blotting, co-immunoprecipitation, and surface plasma resonance spectroscopy. Kinetic analyses showed that the dissociation constant (KD), inhibitory constant (Ki), and half-maximal inhibitory concentration (IC50) were 1.79 × 10(-8) M, 250 pM, and 18.31 pM, respectively, suggesting that vWF binds to eNOS with a high affinity and greater efficacy for activator (insulin) inhibition. These results indicated that vWF, an antagonist of eNOS, inhibits insulin-induced NO production and causes IR.


Developmental trajectories of mobility and self-care capabilities in young children with cerebral palsy.
To describe development of mobility and self-care capabilities in young children (aged 1-4 years) with cerebral palsy, and to examine whether the development of mobility and self-care capabilities differs by cerebral palsy severity in terms of 5 distinct Gross Motor Function Classification System (GMFCS) levels. This prospective longitudinal cohort study included 100 children with cerebral palsy (aged 1.5 or 2.5 years at baseline) and their parents. Mobility and self-care capabilities were assessed by the Pediatric Evaluation of Disability Inventory during yearly assessments from inclusion up to age 4.5 years. Longitudinal data for 92 children were available for analysis. Repeated-measures analyses with random coefficient analysis were performed using linear mixed models. Despite large variations among individuals in the development of mobility and self-care capabilities in young children with cerebral palsy, distinct developmental trajectories were found for children in different GMFCS levels. The estimated change per month differed significantly by GMFCS level for both outcomes. This longitudinal study provides an evidence base for prognosis in daily mobility and self-care skills in young children with cerebral palsy. The developmental trajectories for GMFCS levels can be helpful in communication between professionals and also in discussions of expectations and goal setting with families regarding mobility and self-care in the daily life of young children with cerebral palsy in neonatal follow-up and pediatric practice.


Temporary placement of a paclitaxel or rapamycin-eluting stent is effective to reduce stenting induced inflammatory reaction and scaring in benign cardia stricture models.
To investigate whether temporary placement of a paclitaxel or rapamycin eluting stent is more effective to reduce stenting induced inflammatory reaction and scaring than a bared stent in benign cardia stricture models. Eighty dog models of stricture were randomly divided into a control group (CG, n=20, no stent insertion), a bare stent group (BSG, n=20), a paclitaxel eluting (Pacl-ESG, n=20) and a rapamycin eluting stent group (Rapa-ESG, n=20), with one-week stent retention. Lower-oesophageal-sphincter pressure (LOSP), 5-minute barium height (5-mBH) and cardia diameter were assessed before, immediately after the procedure, and regularly for 6 months. Five dogs in each group were euthanized for histological examination at each follow-up assessment. Stent insertion was well tolerated, with similar migration rates in three groups. At 6 months, LOSP and 5-mBH improved in Pacl-ESG and Rapa-ESG compared to BSG (p<0.05), with no difference between Pacl-ESG and Rapa-ESG (p>0.05). Cardia kept more patency in the Pacl-ESG and Rapa-ESG than in BSG (p<0.05). Reduced peak inflammatory reactions and scarring occurred in the Pacl-ESG and Rapa-ESG compared to BSG (p<0.05), with a similar outcome in the Pacl-ESG and Rapa-ESG (p>0.05). Paclitaxel or rapamycin-eluting stents insertion led to better outcomes than bare stents in benign cardia stricture models.


Pain reactivity in Alzheimer patients with different degrees of cognitive impairment and brain electrical activity deterioration.
Pain perception and autonomic responses to pain are known to be altered in dementia, although the mechanisms are poorly understood. We studied patients with Alzheimer's disease (AD) whose cognitive status was assessed through the Mini Mental State Examination test and whose brain electrical activity was measured by means of quantitative electroencephalography. After assessment of both cognitive impairment and brain electrical activity deterioration, these patients underwent sensory measurements in which the minimum stimulus intensity for both stimulus detection and pain sensation was determined. In addition, heart rate responses to pain threshold x 1.5 were recorded. We found that neither stimulus detection nor pain threshold was correlated to cognitive status and brain electrical activity decline. By contrast, we found a correlation between heart rate responses and deterioration of both cognitive functions and brain electrical activity. In particular, the heart rate increase after pain stimulation was correlated to the presence of slow brain electrical activity (delta and theta frequencies). This correlation was also found for the anticipatory heart rate increase just before pain stimulation. These results indicate that pain anticipation and reactivity depend on both the cognitive status and the frequency bands of the electroencephalogram, whereas both stimulus detection and pain threshold are not affected by the progression of AD. These findings indicate that, whereas the sensory-discriminative components of pain are preserved even in advanced stages of AD, the cognitive and affective functions, which are related to both anticipation and autonomic reactivity, are severely affected. This sensory-affective dissociation is well correlated with the neuropathological findings in AD.


Adaptation at specific loci. VII. Natural selection, dispersal and the diversity of molecular-functional variation patterns among butterfly species complexes (Colias: Lepidoptera, Pieridae).
Natural genetic variants at the phosphoglucose isomerase, PGI, gene differ in spatial patterning of their polymorphism among species complexes of Colias butterflies in North America. In both lowland and alpine complexes, molecular-functional properties of the polymorphic genotypes can be used to predict genotype-specific adult flight performances and resulting large genotypic differences in adult fitness components. In the lowland species complex, there is striking uniformity of PGI polymorph frequencies at a number of sites across the American West; this fits with earlier findings of strong, similar differences in fitness components over this range. In an alpine complex, Colias meadii shows similar uniformity of PGI frequencies within habitat types, either montane steppe or alpine tundra, over several hundred kilometres in the absence of dispersal. At the same time, large shifts (10-20%) in frequency of the most common alleles occur between steppe and tundra populations, whether these are isolated or, as in some cases, are in contact and exchange many dispersing adults each generation. Data on male mating success of common C. meadii PGI genotypes in steppe and tundra show heterozygote advantage in both habitat types, with shifts in relative homozygote disadvantage between habitats which are consistent with observed frequency differences. Nonadaptive explanations for this situation are rejected, and alternative, thermal-ecology-based adaptive hypotheses are proposed for later experimental test. These findings show that strong local selection may dominate dispersal as an evolutionary agent, whether or not dispersal is present, and that selection may often be the major force promoting 'cohesion' of species over long distances. This case offers new opportunities for integrating studies of molecular structure and function with ecological aspects of natural selection in the wild, both within and among species.


Optimization of gene transfer using cationic lipids in cell lines and primary human CD4+ and CD34+ hematopoietic cells.
Cationic lipids offer several advantages for gene delivery, both in vitro and in vivo. However, high-efficiency gene transfer has been demonstrated only for limited cell types. Here, we examine the level of expression of a luciferase reporter gene, delivered using cationic lipids, in both cell lines and primary human cells including peripheral blood mononuclear cells and CD34(+)-enriched hematopoietic cells. Variables shown to affect the efficiency of gene expression included the type of lipid, the amounts of DNA and lipid, the day of assay following transfection, the media used for lipid:DNA complex formation, the cell number, the promoter driving expression of the reporter gene and the physiological state of the cells (e.g., whether or not cells were differentiated). The maximal luciferase expression observed with the primary cells was one to two orders of magnitude lower than that seen in cell lines. Further studies, possibly involving altering the growth conditions for the cells, or using episomal vectors that will allow extrachromosomal maintenance of the DNA, are required to improve the level of transgene expression in the primary human cell types used here.


Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center.
The incidence of early onset colorectal cancer (EOCRC) is rapidly increasing, but there remains paucity of outcome data for young CRC patients. We reviewed the characteristics and outcomes of 241 adults, age <50, who were diagnosed with EOCRC between January 2009 and December 2014. Median age was 42, 56% were male, and 7% had hereditary etiology. Seventy percent had left-sided primaries. At diagnosis, 11%, 50%, and 39% had stage II, III, and IV CRC. Of the patients with stage II and III CRC who underwent curative surgery, 60% and 88% had adjuvant chemotherapy, with 5-year relapse free survival of 82% and 74% respectively. Of the 123 patients with metastatic (m) EOCRC, 93%, 63%, 33%, and 12% had 1st, 2nd, 3rd, and 4th line systemic anticancer therapy (SACT) respectively. For first line SACT, 99% had doublet chemotherapy, with bevacizumab or an anti-EGFR antibody in 57%. Median overall survival (mOS) of mEOCRC patients was 20.1 months (95% C.I: 15.9-23.2). Younger age and signet cells were associated with shorter mOS, whereas more lines of SACT and curative metastasectomy with longer mOS. Metastatic EOCRC patients had poorer outcomes than expected, despite optimal multimodality treatment. This suggests an aggressive disease biology that warrants further research and therapy development.


Seroprevalence of Bartonella spp. infection in HIV patients in Catalonia, Spain.
Although the first clinical descriptions of Bartonella infection were associated with immunocompromised patient with bacillary angiomatosis, we currently know that this organism is directly involved in diseases affecting a large number of patients, regardless of their immune status. Cat scratch disease, hepatic peliosis, and some cases of bacteraemia and endocarditis, are directly caused by some species of the genus Bartonella. The purpose of this study was to determinate the prevalence of IgG antibodies against Bartonella henselae and B. quintana in HIV patients and to identify the epidemiological factors involved. Serum samples were collected from HIV patients treated at Hospital de Sabadell. Antibodies to B. henselae and B. quintana from 340 patients were examined by indirect immunofluorescence assay (IFA). Significance levels for univariate statistical test were determined by the Mann-Whitney U test and chi2 test. Of 340 patients, 82 were women and 258 men, with a median age of 42.21 +/- 10.35 years (range 16-86 years). Seventy-six (22.3%) patients reacted with one or more Bartonella antigens. Of all the factors concerning the seroprevalence rate being studied (age, sex, intravenous drugs use, alcohol consumption, CD4 levels, AIDS, HCV, HBV, residential area), only age was statistically significant. A high percentage of HIV patients presents antibodies to Bartonella and is increasing with age.


Automatic 2-D/3-D Vessel Enhancement in Multiple Modality Images Using a Weighted Symmetry Filter.
Automated detection of vascular structures is of great importance in understanding the mechanism, diagnosis, and treatment of many vascular pathologies. However, automatic vascular detection continues to be an open issue because of difficulties posed by multiple factors, such as poor contrast, inhomogeneous backgrounds, anatomical variations, and the presence of noise during image acquisition. In this paper, we propose a novel 2-D/3-D symmetry filter to tackle these challenging issues for enhancing vessels from different imaging modalities. The proposed filter not only considers local phase features by using a quadrature filter to distinguish between lines and edges, but also uses the weighted geometric mean of the blurred and shifted responses of the quadrature filter, which allows more tolerance of vessels with irregular appearance. As a result, this filter shows a strong response to the vascular features under typical imaging conditions. Results based on eight publicly available datasets (six 2-D data sets, one 3-D data set, and one 3-D synthetic data set) demonstrate its superior performance to other state-of-the-art methods.


Autosomal dominant rolandic epilepsy with speech dyspraxia.
Autosomal Dominant Rolandic Epilepsy with Speech Dyspraxia (ADRESD) is a rare disorder which highlights the relationship between Benign Rolandic Epilepsy (BRE) and speech and language disorders. Subtle speech and language disorders have recently been well characterised in BRE. ADRESD is associated with long term, more severe speech and language difficulties. The time course of rolandic epilepsy in ADRESD is typical of that of BRE. ADRESD is inherited in an autosomal dominant manner with anticipation. It is postulated that the anticipation may be due to an, as yet unidentified, triplet repeat expansion in a gene for rolandic epilepsy. BRE follows complex inheritance but it is possible that ADRESD may hold some valuable clues to the pathogenesis of BRE.


Tobacco use among immigrant and nonimmigrant adolescents: individual and family level influences.
To identify individual and family level characteristics that might explain differences in rates of tobacco use among immigrant and nonimmigrant adolescents. Data for analysis come from a probability sample of 5401 adolescents aged 12-18 years participating in the Ontario Health Survey (OHS). Three groups were compared: (a) adolescents born in Canada to Canadian-born parents (n = 3886), (b) adolescents born in Canada to immigrant parents (n = 1233), and (c) adolescents born outside of Canada (n = 282). Discrete, multilevel logistic regression was used in the analysis. Adolescents born outside of Canada report the lowest rates of tobacco use, despite greater economic hardship. A negative association emerges between family socioeconomic status and tobacco use among adolescents born in Canada but not among adolescents born outside of Canada. Immigrant youth are less likely to affiliate with peers who smoke and are more likely to come from families where parents do not smoke: these differences partially explain the decreased rates of tobacco use among immigrant adolescents. Although subject to greater economic hardship, immigrant youth are less likely to engage in tobacco use. Protective factors associated with immigrant family life, such as lower rates of parental tobacco use and less exposure among immigrant adolescents to peers who smoke, may counteract some of the negative effects of poverty and social hardship. Future research should begin to address the processes that lead to adaptive outcomes among adolescents from immigrant families, despite greater exposure to social disadvantage.


A ferrocenyl kaleidoscope: slow interconversion of six diastereo-atropisomers of 2,6-di-tert-butyl-9,10-diferrocenyltriptycene.
The title triptycene, 6, has been isolated as the product of 9,10-cycloaddition of benzyne to 9,10-diferrocenyl-2,6-di-tert-butylanthracene, 5, whose X-ray crystal structure is reported. Each ferrocenyl unit in 6 has access to the same three non-equivalent molecular environments, and their rotations relative to the molecular paddlewheel give rise to six slowly interconverting atropisomers. Their dynamic behaviour in solution is a challenging NMR puzzle that can be successfully solved by taking advantage of the recently described very large diamagnetic anisotropy of the ferrocenyl moiety, together with the C2 symmetry of particular atropisomers. Application of one- and two-dimensional NMR techniques over a range of temperatures together, with a detailed analysis of the homo- and heteronuclear correlations in 6, resulted in unequivocal mapping of the 99 (1)H and 162 (13)C positions in the six interconverting systems. Variable-temperature 2D-EXSY measurements revealed that, while the stability of the atropisomers is almost identical, they are separated by energy barriers which the ferrocenyls must overcome in the course of their interconversions. The heights of two different rotational barriers have been identified and these experimental findings are in good agreement with DFT calculations.


Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus.
During patient colonization, Staphylococcus aureus is able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased shRNA screening coupled with ultra-fast sequencing to screen 16,000 human genes during S. aureus infection and we identified several host genes important for this intracellular pathogen. In addition, we interrogated our screening results to find novel host-targeted therapeutics against intracellular S. aureus. We found that silencing the human gene TRAM2 resulted in a significant reduction of intracellular bacterial load while host cell viability was restored, showing its importance during intracellular infection. Furthermore, TRAM2 is an interactive partner of the endoplasmic reticulum SERCA pumps and treatment with the SERCA-inhibitor Thapsigargin halted intracellular MRSA survival. Our results suggest that Thapsigargin could be repurposed to tackle S. aureus host cell infection in combination with conventional antibiotics.


River organic matter shapes microbial communities in the sediment of the Rhône prodelta.
Microbial-driven organic matter (OM) degradation is a cornerstone of benthic community functioning, but little is known about the relation between OM and community composition. Here we use Rhône prodelta sediments to test the hypothesis that OM quality and source are fundamental structuring factors for bacterial communities in benthic environments. Sampling was performed on four occasions corresponding to contrasting river-flow regimes, and bacterial communities from seven different depths were analyzed by pyrosequencing of 16S rRNA gene amplicons. The sediment matrix was characterized using over 20 environmental variables including bulk parameters (for example, total nitrogen, carbon, OM, porosity and particle size), as well as parameters describing the OM quality and source (for example, pigments, total lipids and amino acids and δ(13)C), and molecular-level biomarkers like fatty acids. Our results show that the variance of the microbial community was best explained by δ(13)C values, indicative of the OM source, and the proportion of saturated or polyunsaturated fatty acids, describing OM lability. These parameters were traced back to seasonal differences in the river flow, delivering OM of different quality and origin, and were directly associated with several frequent bacterial operational taxonomic units. However, the contextual parameters, which explained at most 17% of the variance, were not always the key for understanding the community assembly. Co-occurrence and phylogenetic diversity analysis indicated that bacteria-bacteria interactions were also significant. In conclusion, the drivers structuring the microbial community changed with time but remain closely linked with the river OM input.