Longitudinal consistency of the relationship between depression symptoms and cognitive functioning in multiple sclerosis.
Lifetime prevalence rates of cognitive dysfunction and depression in multiple sclerosis (MS) have typically been reported to be approximately 50 percent. However, an inconsistent relationship between these two common features of MS has been reported in the literature. Because neurovegetative depression symptoms overlap with MS symptoms, it may be that literature inconsistencies can partly be explained by the fact that only those depression symptom clusters unambiguously reflective of depression are associated with cognitive dysfunction. To explore the relationship between different depression symptom clusters and a battery of tests measuring cognitive domains commonly impaired in MS and was examined at two time points 3 years apart. The Chicago Multiscale Depression Inventory was employed to measure mood, negative evaluative, and neurovegetative symptom clusters in 53 MS patients who were also administered a battery of neuropsychological tests. At time point 1, Mood and Evaluative Chicago Multiscale Depression Inventory scales were significantly associated with tasks of complex speeded attention, planning, and working memory. At time point 2, the Evaluative scale was still significantly associated with these domains, in addition to spatial memory; however, all of the significant correlations with the Mood scale dropped out. These results show that negative evaluative depression symptoms are most consistently predictive of cognitive dysfunction in MS. It may be that negative evaluative depression symptoms use up available cognitive capacity, thus compromising performance on cognitive capacity demanding tasks in MS patients.


[The steroid hormone levels and receptors of steroid hormone receptors in rat muscles during physical exertion].
It is shown that the testosterone content in skeletal muscles of female albino rats is 2-fold decreased, while the estradiol content-1.5-fold increased and progesteron content showed no changes after systematic physical exercises. The pharmacokinetic investigations showed that androgen half-life in the organism decreased from 8 to 5 h under physical exercises. The amount of androgen receptors in cytosol of skeletal muscles increases from 1.34 +/- 0.08 to 1.71 +/- 0.10 fmol/mg per 1 mg of protein. Kd is 0.40 +/- 0.03 and 0.48 +/- 0.08 nM, respectively. Sensitivity of the organism to hormonal signal play an important role in the metabolism regulation in skeletal muscles along with the hormonal content change during the organism adaptation to physical exercises.


[From "acute AIDS" to "chronic AIDS": body perception and surgical interventions in people living with HIV and AIDS].
The Brazilian government has been providing free and universal access to the HAART therapy for people living with HIV and AIDS for ten years. Since then, many epidemiological characteristics have changed, and AIDS passed scientifically and medically to be classified as a chronic condition. This qualitative study aims to comprehend the challenges posed by self-perception of body changes experienced by people living with AIDS during recent years, as a result of prolonged use of antiretroviral medication.With this purpose, in 1999 and 2005, 32 semi-structured interviews with HIV positive individuals were held in the State of Sao Paulo to capture the challenges occurred during this period, in particular with regard to the lipodystrophy syndrome. The analysis of the data indicates that even with the availability and use of new technologies that allowed for AIDS to transform into a chronic, clinically treatable disease, there are still important aspects lived by patients that reedit fears and difficulties similar to those of the initial periods of the epidemic, among others appearance-impairing physical stigma.


TRPs in our senses.
In the last decade, studies of transient receptor potential (TRP) channels, a superfamily of cation-conducting membrane proteins, have significantly extended our knowledge about the molecular basis of sensory perception in animals. Due to their distinct activation mechanisms and biophysical properties, TRP channels are highly suited to function in receptor cells, either as receptors for environmental or endogenous stimuli or as molecular players in signal transduction cascades downstream of metabotropic receptors. As such, TRP channels play a crucial role in many mammalian senses, including touch, taste and smell. Starting with a brief survey of sensory TRP channels in invertebrate model systems, this review covers the current state of research on TRP channel function in the classical mammalian senses and summarizes how modulation of TRP channels can tune our sensations.


Enhanced protein expression by internal ribosomal entry site-driven mRNA translation as a novel approach for in vitro loading of dendritic cells with antigens.
Transfection of dendritic cells (DCs) with messenger RNAs (mRNAs) of tumor-associated antigens (TAAs) is a promising strategy for cancer vaccines. TAA mRNA can be generated by in vitro transcription using DNA encoding the TAA gene as a template. A cap analog is usually added upon in vitro transcription to stabilize mRNA and enhance the efficiency of mRNA translation. However, the inclusion of the cap analog correlates with significantly lower-yield mRNA transcription, potentially leading to an expensive vaccine manufacturing process. To solve this problem, we present a novel approach in which DNA templates are modified with an internal ribosomal entry site (IRES) sequence inserted upstream of the gene of interest to replace the use of the cap analog. The presence of IRES greatly enhanced transcription for the mRNA in vitro compared with the cap analog. Also, higher transgene expression was achieved using luciferase (Luc) mRNA with IRES than using capped Luc mRNA to transfect DCs. Immunization of mice with DCs transfected with IRES-containing mRNA encoding chicken ovalbumin (OVA) induced significant levels of antigen-specific interferon gamma-producing CD8(+) T cells and in vivo killing of antigen-bearing cells. Consistently, mice immunized with IRES-containing OVA mRNA-transfected DCs were protected from pulmonary metastasis of melanoma cells injected intravenously. We suggest that IRES can be used for the production of larger quantities of mRNA and that such IRES-containing mRNAs may be useful for DC-based antitumor immunotherapy.


Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias.
Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant of acute promyelocytic leukemia, resistant to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells. We identified a subset of cells resistant to RA with proliferation, DNA replication, and repair signatures that depend on a fine-tuned E2F transcriptional network targeting the epigenetic regulator enhancer of zeste homolog 2 (EZH2). Epigenomic and functional analyses validated the driver role of EZH2 in RA resistance. Targeting pan-EZH2 activities (canonical/noncanonical) was necessary to eliminate leukemia relapse-initiating cells, which underlies a dependency of resistant cells on an EZH2 noncanonical activity and the necessity to degrade EZH2 to overcome resistance. Our study provides critical insights into the mechanisms of RA resistance that allow us to eliminate treatment-resistant leukemia cells by targeting EZH2, thus highlighting a potential targeted therapy approach. Beyond RA resistance and acute promyelocytic leukemia context, our study also demonstrates the power of single-cell multiomics to identify, characterize, and clear therapy-resistant cells.


Body mass index, sexual behaviour, and sexually transmitted infections: an analysis using the NHANES 1999-2000 data.
Factors determining human sexual behaviour are not completely understood, but are important in the context of sexually transmitted disease epidemiology and prevention. Being obese is commonly associated with a reduced physical attractiveness but the associations between body mass index, sexual behaviour and the risk of acquiring sexually transmitted infections has never been studied. The National Health and Nutrition Examination Survey (NHANES) files of 1999-2000 were used. Linear regression was used to relate the reported number of sex partners in the last year and lifetime to Body Mass Index (BMI). Logistic regression was used to relate Herpes Simplex Virus type II (HSV-2) antibodies to BMI and other variables. Data on 979 men and 1250 women were available for analysis. Obese (mean number of partners for men:1.12, women: 0.93) and overweight (mean for men: 1.38, women: 1.03) individuals reported fewer partners than individuals of normal BMI (mean for men: 2.00, women: 1.15) in the last year (p < .0.01 & p < 0.05 for men, p < 0.05 & n.s. for women). The same relationship held for lifetime partners in men (mean 11.94, 18.80, and 22.08 for obese, overweight and normal BMI respectively (p < 0.05 & n.s. for obese and overweight vs normal respectively), but not in women (mean 7.96, 4.77, and 5.24 respectively). HSV-2 antibodies were significantly correlated with the number of lifetime partners in both men and women, with the odds of being HSV-2 positive increasing by 0.6% (p < 0.01) and 2.7% (p < 0.01) for men and women respectively. HSV-2 antibodies increased with age, even after adjustment for lifetime partners (p < 0.01). Being obese (HSV-2 prevalence 15.9 and 34.9% for men and women respectively) or overweight (HSV-2 prevalence 16.7 and 29.3 for men and women respectively) was not associated with HSV-2 antibodies (HSV-2 prevalence for normal BMI: 15.6 and 23.2% respectively), independent of whether the association was adjusted for life time sexual partners or not. There was evidence of substantial misreporting of sexual behaviour. Obese and overweight individuals, especially men, self report fewer sex partners than individuals of normal weight, but surprisingly this is not reflected in their risk of HSV-2 infection. HSV-2 antibodies provide information not contained in self-reported number of partners and may better estimate sexual risk than self-reported behaviour.


Dental Implant Outcomes in Grafted Sockets: a Systematic Review and Meta-Analysis.
To assess the treatment outcomes of the dental implants placed in the grafted sockets. A search protocol was developed to evaluate the treatment outcomes of dental implants placed in the grafted sockets in terms of implant survival rates (primary outcome), marginal-bone-level (MBL) changes, clinical parameters (i.e., bleeding on probing, probing depth), occurrence of peri-implant diseases, and aesthetic outcomes (secondary outcomes). Randomized controlled clinical trials (RCTs), controlled clinical trials, and prospective studies with at least 12 months of follow-up and a minimum of 10 patients having at least one dental implant inserted into the grafted socket were conducted. MEDLINE (PubMed) was searched for relevant articles published until 1st April 2019. A meta-analysis was performed using the random-effects model on the selected qualifying articles. The present analysis included 7 RCTs. The survival rate of the implants inserted into the grafted sockets ranged from 95 to 100% after 1 to 4 years of follow-up. MBL loss was found to be significantly greater for the implants placed in the non-grafted healed sites than for those placed in the previously grafted sockets (weighted mean difference = -1.961 mm, P < 0.0001). In terms of MBL changes, no difference was detected between immediately inserted implants versus implants placed in previously grafted sockets. None of the included studies reported on the clinical parameters or occurrence of peri-implant diseases. Implants inserted into the previously grafted sockets showed high survival rates and lower marginal-bone-level loss than the implants inserted into the non-grafted sites.


The relationship between body structure and the socio-economic status in Hungarian children and adolescents.
Among the numerous factors that influence the pattern of children's growth and development there are factors of the changeable socio-economic environment. The inequalities among the socio-economic strata in the Hungarian society have increased during last decades. The main objective of the study was to examine the body structure of children and adolescents living in different socio-economic backgrounds. The subjects of the present paper (9479 boys, 9304 girls) were examined in the 2nd Hungarian National Growth Study 2003-2006. Body structure was assessed by some absolute body dimensions, BMI, body composition and body shape indices. Children were grouped into relatively good, average and poor socio-economic subgroups by considering the education and occupation of the parents as well as the number of children in the family. Significant differences were found in the body structure of children varying in the socio-economic background: the better the socio-economic conditions the higher stature in both genders, while the lower relative fatness was found only in pubertal girls. The prevalence of unhealthy nutritional statuses (both underweight and overweight/ obese) was significantly lower in children living in better socio-economic conditions in both genders. Differences that were found in the body structure of children living in different socio-economic backgrounds emphasize the importance of using reference growth values layered also to socio-economic strata for screening nutritional status in childhood and adolescence.


Successful percutaneous endovascular treatment of a ruptured femoral aneurysm.
Popliteal and femoral aneurysms account for about 70% of the incidence of peripheral aneurysms. Only 4% of aneurysms run their course with the clinical evidence of rupture. The ruptured aneurysm is dangerous because of a potential limb loss as well as due to the threat of lethal outcome in patients at a high surgical risk. Presented herein is a successful experience (first in this country) gained with the treatment of a ruptured femoral aneurysm by means of endoprosthetics using a new stent graft with PTFB coating in a patient at a high risk for traditional surgical treatment.


[Presence of lipofuscin masses in the myocardium of Torpedo m].
Using histochemical and fluorescence microscope techniques (400-470 nm) lipofuscin masses have been found in the myocardium od Torpedo m., thereby confirming that the senescence pigment is a debris material. Future studies will better characterise the ultrastructure and the biochemical composition of these masses.


The use of midazolam and opioid associations in anesthesia (ataranalgesia).
Ataranalgesia (ATA) is realized by the association of a strong morphinomimetic, a benzodiazepine (BZD) and a curare. It is an anesthesia technique derived from neuroleptanalgesia, one of the most employed modern anesthesia techniques. In this formula, midazolam, a hydrosoluble BZD, with a rapid onset of action and a shorter duration of action than the other substances of this group (diazepam or flunitrazepam) was rapidly introduced. For the induction of an ATA, we mix in the same syringe the loading doses of the BZD, the opiate (fentanyl, alfentanil or sulfentanil) and the curare (pancuronium or atracurium) and we administer them simultaneously. The maintenance of anesthesia is performed by perfusion of the opioid with a constant flow, deliberately underdosed, in addition to microboli of the 3 chosen substances as needed to assure the stability of anesthesia. In this anesthesia mixture, midazolam ensures sedation, sleep, amnesia and reinforces and stabilizes the analgesic or myorelaxant action of the two other substances. To realize this technique with success, it is useful to remember the pharmacological interactions that are created between midazolam, the morphinomimetics and the curare. This report will focus on their description. The possibilities to use midazolam in anesthesia and the controllability of ATA have been enlarged since the synthesis of the antidote Ro 15-1788 (Anexate).


The ego, the ocular, and the uncanny: why are metaphors of vision central in accounts of the uncanny?
I am my own twin, Always with me, same as me, and always watching me! From interview with a psychotic patient Every man carries with him through life a mirror, as unique and impossible to get rid of as his shadow W.H. Auden, 1989, p.93 I cannot urge you too strongly to a meditation on optics. Jacques Lacan, 1991, p.76 This paper outlines the basic arguments for a reading of the notion of the uncanny that draws on direct and metaphorical significances of the ocular in the development of human ego. It is argued that a specular-oriented reading of the uncanny as made possible through Lacan's model for ego development introduces a significant analytic device capable of explaining diverse features of the uncanny experience that escaped the traditional phallic/castration-based reading. To examine this claim, evidence is presented from a number of contexts to demonstrate how uncanny experiences are typically constructed through and associated with themes and metaphors of vision, blindness, mirrors and other optical tropes. Evidence is also presented from a historical point of view to demonstrate the strong presence of ocular and specular themes, devices and associations in a tradition of literary and psychological writing out of which the notion of 'the uncanny' (including Freud's own formulation) emerged. It is demonstrated that the main instances of the uncanny, such as doppelgangers, ghosts, déjà vu, alter egos, self-alienations and split personhoods, phantoms, twins, living dolls and many more in the list of 'things of terror' typically share two important features: they are closely tied with visual tropes, and they are variations on the theme of doubling. It is then argued that both of these features are integrally associated with the developmental processes of ego formation and self-identity, thus explaining the strong association of the uncanny accounts and experiences with ocular and specular motifs and metaphors.


A Natural Compound Containing a Disaccharide Structure of Glucose and Rhamnose Identified as Potential N-Glycanase 1 (NGLY1) Inhibitors.
N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.


Pemphigus vulgaris: case report in a Nigerian Negro.
A middle-aged Nigerian male had generalised pruritus, widespread flaccid vesicles and bullae, with ulcerations of the skin that heal without scarring, weight loss, positive nikolsy sign, anaemia, and marked eosinophilia. Pemphigus vulgaris is a rare disease among those of Negroid extraction, we therefore, report this case involving a Nigerian.


Oral rosmarinic acid-enhanced Mentha spicata modulates synovial fluid biomarkers of inflammation in horses challenged with intra-articular LPS.
A biological extract of high-rosmarinic acid mint (HRAM) has previously demonstrated inhibitory effects on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)), nitric oxide (NO) and glycosaminoglycan (GAG) release in vitro. This study was undertaken to determine whether HRAM added to feed produces similar effects in horses challenged with intra-articular LPS. Eight horses received HRAM (0 or 28.1 ± 1.3 g/day; n = 4 per group) in their feed for 24 days in a blinded manner. On day 21, all horses received an intra-articular injection of LPS (0.3 ng) into their left or right intercarpal joint. Synovial fluid (SF) samples were taken on postinjection day (PID)-21 (i.e. prior to commencement of supplementation), PID0, PID0.25, PID0.5, PID1 and PID3 and analysed for PGE(2), GAG, NO, protein and total nucleated cells counts. Blood biochemistry and haematology screens were conducted at PID-21, PID0, PID1 and PID3. There was a significant reduction in LPS-induced PGE(2) and GAG in SF in horses supplemented with HRAM compared with controls and a tendency to increase complement recognition protein accumulation in synovial fluid of HRAM horses. Plasma from HRAM horses had reduced total white blood cells, segmented neutrophils (compared with baseline concentrations) and lymphocytes (compared with controls), and increased SF nucleated cell count (compared with baseline concentrations and controls). It is concluded that HRAM offered as part of the feed alter biomarkers of inflammation in SF of LPS-challenged horses. Larger studies that seek to clarify effects of HRAM on synovial fluid cell counts and possible role of HRAM-induced interference with complement signalling are warranted.


Networking and rheology of concentrated clay suspensions "matured" in mineral medicinal water.
This work studied the influence of "maturation" conditions (time and agitation) on aggregation states, gel structure and rheological behaviour of a special kind of pharmaceutical semisolid products made of concentrated clay suspensions in mineral medicinal water. Maturation of the samples was carried out in distilled and sulphated mineral medicinal water, both in static conditions (without agitation) and with manual stirring once a week, during a maximum period of three months. At the measured pH interval (7.5-8.0), three-dimensional band-type networks resulting from face/face contacts were predominant in the laminar (disc-like) clay suspensions, whereas the fibrous (rod-like) particles formed micro-aggregates by van der Waals attractions. The high concentration of solids in the studied systems greatly determined their behaviour. Rod-like sepiolite particles tend to align the major axis in aggregates promoted by low shearing maturation, whereas aggregates of disc-like smectite particles did not have a preferential orientation and their complete swelling required long maturation time, being independent of stirring. Maturation of both kinds of suspensions resulted in improved rheological properties. Laminar clay suspensions became more structured with time, independently from static or dynamic maturation conditions, whereas for fibrous clay periodic agitation was also required. Rheological properties of the studied systems have been related to aggregation states and networking mechanisms, depending on the type of clay minerals constituents. Physical stability of the suspensions was not impaired by the specific composition of the Graena medicinal water.


Helicobacter pylori: getting to grips with the guidance.
Helicobacter pylori is a Gram-negative bacterium that inhabits the mucus layer above the gastric mucosa. While infection rates vary by region, the global prevalence is estimated at 50%. While asymptomatic carriage is common, infection can result in significant morbidity and mortality from complications including peptic ulcer disease, atrophic gastritis and gastric cancer. Paediatric and adult practices diverge due to differences in complication rate, symptomatology, practicalities with investigations and treatment options. Widespread use of standard antibiotic regimens has however resulted in a rapid global increase in antibiotic resistance and treatment failure in all ages. There is urgent need to optimise treatment regimens and maximise first-time eradication rates. This need is reflected in the latest guidelines from the European Society for Paediatric Gastroenterology Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for paediatric practice and the Maastricht Guidelines for adult practice. This article aims to provide a practical overview of the investigations and management of H. pylori by comparing and contrasting these guidelines.


The impact of patient education on the quality of inpatient bowel preparation for colonoscopy.
For patients requiring colonoscopy while admitted to hospital, achieving adequate cleansing of the colon is often difficult. To assess the impact of patient education, in the form of both counselling and written instructions, on bowel cleanliness at colonoscopy. A total of 38 inpatients at a tertiary care hospital in Vancouver, British Columbia, who were referred to the gastroenterology service for colonoscopy were enrolled in the present study. Sixteen patients were randomly assigned to the intervention group, while 22 patients comprised the control group. Both groups received a clear liquid diet and 4 L of a commercially available bowel preparation. The intervention group also received a brief counselling session and written instructions outlining the methods and rationale for bowel preparation before colonoscopy. Bowel cleanliness was assessed by the endoscopist using a five-point rating scale. The two groups were similar with respect to demographics, the indication for colonoscopy and findings at colonoscopy. The median bowel cleanliness scores in the control group and the enhanced-instruction group were 3.0 and 2.0, respectively (P=0.001). Patient counselling and written instructions are inexpensive, safe and simple interventions. Such interventions are an effective means of optimizing colonoscopy preparation in the inpatient setting.


Increased tolerance to oxidative stress in transgenic tobacco expressing a wheat oxalate oxidase gene via induction of antioxidant enzymes is mediated by H2O2.
Hydrogen peroxide (H(2)O(2)) plays a key role in the regulation of plant responses to various environmental stresses and modulates the expression of related genes including those encoding antioxidant enzymes. A wheat oxalate oxidase (OxO) gene was transformed and expressed in tobacco for production of H(2)O(2). The transgenic plants exhibited enhanced OxO activities and H(2)O(2) concentrations, which was blocked by inhibitors of OxO. The transgenic plants showed increased tolerance to methyl viologen (MV) or high light-induced oxidative stress in both short-time and long-time tests by measuring their maximal photochemical efficiency of PSII (F(v)/F(m)), ion leakage and malondialdehyde. Higher activities and transcripts of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) were observed in the transgenic plants compared to their wild-type controls under normal growth conditions. Pretreatments with inhibitors of OxO and scavenger of H(2)O(2) blocked the increase of tolerance to MV-induced or high light-induced oxidative stress, as well as the induction of antioxidant enzyme activities. Pretreatments with H(2)O(2) increased tolerance to oxidative stresses and antioxidant enzyme activities. It is suggested that H(2)O(2) produced by OxO in the transgenic tobacco plants triggers the signaling pathways to upregulate expressions of antioxidant enzyme genes, which in turn results in the increase of tolerance to MV-induced and high light-induced oxidative stresses.


[Effect of stress on calcium homeostasis in muscular tissues].
A dynamics of the content of calcium (Ca) in aorta, heart and skeletal muscles was studied in rats exposed to a stress factor for 21 weeks. We observed a 7-fold increase in its content in all the organs examined by the middle of an experiment and its progressive decrease by the 21-st week. It might result from the stages of stress and development of hypercholisterinemia. An inhibitor of L-type calcium channels niphidipine did not change the dynamics of Ca content qualitatively but it decreased its quantitative parameters, especially at final stages of experiments. We suggest that possible mechanism of keeping calcium homeostasis in the organs examined at different stages of stress is an intensive work of ligand- and potential-dependent calcium channels.


Hypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane A2, Ca2+, and superoxide anion levels.
This study investigated the mechanisms underlying the response to hydrogen peroxide (H(2)O(2)) in mesenteric resistance arteries from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) rats. Arteries were mounted in microvascular myographs for isometric tension recording and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)), superoxide anion (O(2)(.)) production was evaluated by dihydroethidium fluorescence and confocal microscopy, and thromboxane A(2) (TXA(2)) production was evaluated by enzyme immunoassay. H(2)O(2) (1-100 microM) induced biphasic responses characterized by a transient endothelium-dependent contraction followed by relaxation. Simultaneous measurements of tension and Ca(2+) showed a greater effect of H(2)O(2) in arteries from hypertensive than normotensive rats. The cyclooxygenase (cox) inhibitor, indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-H-indole-3-acetic acid] (1 microM); the COX-1 inhibitor, SC-58560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole] (1 microM); the thromboxane (TXA(2)) synthase inhibitor, furegrelate [5-(3-pyridinylmethyl)-2-benzofurancarboxylic acid, sodium salt] (10 microM); and the TXA(2)/prostaglandin H(2) receptor antagonist, SQ 29,548 ([1S-[1.alpha.,2.alpha.(Z),3.alpha.,4.alpha.]]-7-[3-[[2-[(phenylamino) carbonyl] hydrazino] methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid)) (1 microM) abolished H(2)O(2) contraction in arteries from WKY rats but only reduced it in SHRs. The O(2)(.) scavenger, tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid disodium salt) (1 mM), and the NADPH oxidase inhibitor, apocynin (4'-hydroxy-3'-methoxyacetophenone) (0.3 mM), decreased H(2)O(2) contraction in arteries from SHRs but not in WKY rats. H(2)O(2) induced TXA(2) and O(2)(.) production that was greater in SHRs than in WKY rats. The TXA(2) analog, U46619 [9,11-di-deoxy-11 alpha,9 alpha-epoxymethano prostaglandin F(2 alpha) (0.1 nM-1 microM)], also increased O(2)(.) production in SHR vessels. H(2)O(2)-induced TXA(2) production was decreased by SC-58560. H(2)O(2)-induced O(2)(.) production was decreased by tiron, apocynin, and SQ 29,548. In conclusion, the enhanced H(2)O(2) contraction in resistance arteries from SHRs seems to be mediated by increased TXA(2) release from COX-1 followed by elevations in vascular smooth muscle [Ca(2+)](i) levels and O(2)(.) production. This reveals a new mechanism of oxidative stress-induced vascular damage in hypertension.


A national surveillance program for evaluating new reagent lots in medical laboratories.
Differences between laboratory results attributable to the use of different reagent lots can potentially affect the diagnosis and monitoring of patients. To minimize patient risks, all laboratories should verify that new reagent lots meet agreed analytical performance specifications (APS). We propose a simplified, pragmatic approach for laboratories that involves compilating results into a national surveillance program, and present the first results obtained when applying this approach to troponins, glycated hemoglobin (HbA1c), prostate-specific antigen (PSA) and D-dimer. In the surveillance program we have (i) determined APS for selected analytes, (ii) implemented a simplified procedure for lot evaluation with patient samples used in laboratories across Norway and (iii) performed central processing of the results from the participating laboratories. Over a one-year period, 27 Norwegian laboratories returned results from 28 lot changes for troponin I, 11 for troponin T, and 29 for HbA1c, PSA and D-dimer. The mean difference between two reagent lots was 4.5% for troponin I (for a concentration interval of 20-32 ng/L), 5.1% for troponin T (10.7-17.5 ng/L), 2.2% for HbA1c (40-50 mmol/mol), 3.7% for PSA (3-5 μg/L) and 5.5% for D-dimer (0.4-1.0 mg/L FEU). A novel procedure for reagent lot evaluation is proposed in which information about multiple lot changes from different medical laboratories can be accumulated nationally. Sharing this information allows simplification of lot evaluations in individual laboratories and provides real-world data about lot-to-lot variations.


Opening up openness: a theoretical sort following critical incidents methodology and a meta-analytic investigation of the trait family measures.
Existing taxonomies of Openness's facet structure have produced widely divergent results, and there is limited comprehensive empirical evidence about how Openness-related scales on existing personality inventories align within the 5-factor framework. In Study 1, we used a critical incidents sorting methodology to identify 11 categories of Openness measures; in Study 2, we meta-analyzed the relationships of these categories with global markers of the Big Five traits (utilizing data from 106 samples with a total sample size of N = 35,886). Our results identified 4 true facets of Openness: aestheticism, openness to sensations, nontraditionalism, and introspection. Measures of these facets were unadulterated by variance from other Big Five traits. Many traits frequently conceptualized as facets of Openness (e.g., innovation/creativity, variety-seeking, and tolerance) emerged as trait compounds that, although related to Openness, are also dependent on other Big Five traits. We discuss how Openness should be conceptualized, measured, and studied in light of the empirically based, refined taxonomy emerging from this research.


Causes and Consequences of Purifying Selection on SARS-CoV-2.
Owing to a lag between a deleterious mutation's appearance and its selective removal, gold-standard methods for mutation rate estimation assume no meaningful loss of mutations between parents and offspring. Indeed, from analysis of closely related lineages, in SARS-CoV-2, the Ka/Ks ratio was previously estimated as 1.008, suggesting no within-host selection. By contrast, we find a higher number of observed SNPs at 4-fold degenerate sites than elsewhere and, allowing for the virus's complex mutational and compositional biases, estimate that the mutation rate is at least 49-67% higher than would be estimated based on the rate of appearance of variants in sampled genomes. Given the high Ka/Ks one might assume that the majority of such intrahost selection is the purging of nonsense mutations. However, we estimate that selection against nonsense mutations accounts for only ∼10% of all the "missing" mutations. Instead, classical protein-level selective filters (against chemically disparate amino acids and those predicted to disrupt protein functionality) account for many missing mutations. It is less obvious why for an intracellular parasite, amino acid cost parameters, notably amino acid decay rate, is also significant. Perhaps most surprisingly, we also find evidence for real-time selection against synonymous mutations that move codon usage away from that of humans. We conclude that there is common intrahost selection on SARS-CoV-2 that acts on nonsense, missense, and possibly synonymous mutations. This has implications for methods of mutation rate estimation, for determining times to common ancestry and the potential for intrahost evolution including vaccine escape.


Translating a National Laboratory Strategic Plan into action through SLMTA in a district hospital laboratory in Botswana.
The Ministry of Health (MOH) of Botswana adopted Strengthening Laboratory Management Toward Accreditation (SLMTA), a structured quality improvement programme, as a key tool for the implementation of quality management systems in its public health laboratories. Coupled with focused mentorship, this programme aimed to help MOH achieve the goals of the National Laboratory Strategic Plan to provide quality and timely clinical diagnoses. This article describes the impact of implementing SLMTA in Sekgoma Memorial Hospital Laboratory (SMHL) in Serowe, Botswana. SLMTA implementation in SMHL included trainings, improvement projects, site visits and focused mentorship. To measure progress, audits using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist were conducted at baseline and exit of the programme, with scores corresponding to a zero- to five-star scale. Turnaround times, customer satisfaction, and several other health service indicators were tracked. The laboratory scored 53% (zero stars) at the baseline audit and 80% (three stars) at exit. Nearly three years later, the laboratory scored 85% (four stars) in an official audit conducted by the African Society for Laboratory Medicine. Turnaround times became shorter after SLMTA implementation, with reductions ranging 19% to 52%; overall patient satisfaction increased from 56% to 73%; and clinician satisfaction increased from 41% to 72%. Improvements in inventory management led to decreases in discarded reagents, reducing losses from US $18 000 in 2011 to $40 in 2013. The SLMTA programme contributed to enhanced performance of the laboratory, which in turn yielded potential positive impacts for patient care at the hospital.


Using artificial intelligence and longitudinal location data to differentiate persons who develop posttraumatic stress disorder following childhood trauma.
Post-traumatic stress disorder (PTSD) is characterized by complex, heterogeneous symptomology, thus detection outside traditional clinical contexts is difficult. Fortunately, advances in mobile technology, passive sensing, and analytics offer promising avenues for research and development. The present study examined the ability to utilize Global Positioning System (GPS) data, derived passively from a smartphone across seven days, to detect PTSD diagnostic status among a cohort (N = 185) of high-risk, previously traumatized women. Using daily time spent away and maximum distance traveled from home as a basis for model feature engineering, the results suggested that diagnostic group status can be predicted out-of-fold with high performance (AUC = 0.816, balanced sensitivity = 0.743, balanced specificity = 0.8, balanced accuracy = 0.771). Results further implicate the potential utility of GPS information as a digital biomarker of the PTSD behavioral repertoire. Future PTSD research will benefit from application of GPS data within larger, more diverse populations.


Nanocoatings containing sulfated polysaccharides prepared by layer-by-layer assembly as models to study cell-material interactions.
The understanding of both cell-extracellular matrix (ECM) and cell-material interactions is crucial for the success of implantable biomaterials including tissue engineering devices. ECM is rich in sulfated and aminated glycosaminoglycans and proteoglycans. The development of synthetic models containing those chemical groups is thus of major interest. Thin coatings of polysaccharides with controlled sulfur and nitrogen contents were developed by layer-by-layer assembly. In particular, the multilayers were prepared by assembling chitosan with κ-, ι- and λ-carrageenan (increasing sulfur content). The nanostructured multilayers were characterized by quartz crystal microbalance with dissipation (QCM-D), atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle, X-ray photoelectron spectroscopy (XPS) and used as models to study the effect of the sulfate groups over the behavior of osteoblast-like cells. The biomimetic coatings increased the alkaline phosphatase (ALP) activity and proliferation compared with unmodified polycaprolactone surfaces. Biomineralization increase with the presence of the coatings is significantly higher on ι-carrageenan coatings, suggesting that the sulfate groups may interact positively with molecules involved in the osteoblastic activity as it occurs in the natural ECM. The developed nanocoatings can constitute an interesting model to understand the biological influence of the sulfate and amine groups existing on the surface of biomaterials.


Leptospirosis: a globally increasing zoonotic disease.
A 27-year-old previously healthy man was admitted to the intensive care unit with severe jaundice, dyspnoea with haemoptysis, anaemia, thrombocytopenia and acute renal injury. He had no recent history of foreign travel but had been building a shed in his back garden in Cork, Ireland, for the preceding week. The patient's history, clinical observations, haematological and radiological results were all consistent with icteric leptospirosis or Weil's disease. This was confirmed on serological testing. He completed 7 days intravenous ceftriaxone and made a complete recovery. While endemic in tropical climates, leptospirosis incidence is increasing in temperate climates. Recent cases seen in temperate climates can be severe, particularly with pulmonary manifestations. The report of this case serves to increase awareness of this re-emerging potentially fatal infectious disease.


Adaptation of the Shoulder Disability Questionnaire to the Turkish population, its reliability and validity.
The objective of this study was to adapt the Shoulder Disability Questionnaire (SDQ) for use in Turkey, and to test its reliability and validity. Eighty patients with shoulder pain were included in the study. Pain severity at rest, with motion and during sleeping was assessed by using a numeric pain scale. The shoulder's active and passive range of motion were measured by a goniometer and recorded. The Constant-Murley scale was used for functional assessment. The Turkish version of the SDQ, which was adapted by using guidelines, was completed by the patients. To assess reproducibility, the SDQ was completed by 32 patients who did not improve 1 week later. The reliability of the adapted version was good, with high internal consistency (Cronbach's alpha=0.76) and test-retest reliability (Pearson's correlation coefficient=0.88). The Turkish version of the SDQ was found to have a moderate correlation with pain at rest, with motion and during sleeping. The Turkish version of the SDQ was found to be reliable and valid. The moderate correlation of the questionnaire with clinical parameters including pain shows its validity, but the questionnaire should be tested extensively for detecting changes within time, for use in the follow-up and clinical practice.


Periprocedural Nebivolol for the Prevention of Contrast-Induced Acute Kidney Injury: A Systematic Review and Meta-analysis.
Nebivolol provides a protective effect on contrast-induced acute kidney injury (CIAKI) in animal models. However, the reports on the efficacy of nebivolol for the prevention of CIAKI in human remain unclear. The objective of this meta-analysis was to assess the effect of nebivolol for the prevention of CIAKI. Comprehensive literature searches were performed using MEDLINE, EMBASE, and Cochrane Database from inception through February 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of CIAKI in patients who received nebivolol versus those who did not were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Four studies (2 randomized controlled trials and 2 cohort studies) with 543 patients were included in our analysis to assess the risk of CIAKI and the use of nebivolol. Patients in the nebivolol group had an overall lower incidence of CIAKI (14.4%) compared to the control group (18.4%). The pooled RR of CIAKI in patients receiving nebivolol was 0.66 (95% CI: 0.38-1.15, I (2) = 0). When meta-analysis was limited only to randomized control trials (RCTs), the pooled RR of CIAKI in patients receiving nebivolol was 0.79 (95% CI: 0.35-1.79, I (2) = 0%). Despite no statistical significance, there was a trend toward reduced CIAKI risk in patients receiving nebivolol. The findings of our meta-analysis suggest the need of a large RCT with very careful attention to the balance of benefits and harms.


Small hepatocellular carcinoma: MRI findings for predicting tumor growth rates.
Current clinical practice favors imaging rather than biopsy to diagnose hepatocellular carcinoma (HCC). There is a need to better understand tumor biology and aggressiveness of HCC. Our goal is to investigate magnetic resonance imaging (MRI) features of HCC that are associated with faster growth rates (GRs). After approval from institutional review board, a retrospective evaluation was performed of pre-liver transplant patients. Fifty-two patients who developed a >2 cm HCC on serial imaging were included in the study group, with a total of 60 HCCs seen. Precursor foci were identified on serial MRIs before the specific diagnostic features of >2 cm HCC could be made, and GRs and MRI features, including signal on T1- and T2-weighted images (WI), the presence of intralesional steatosis on chemical shift imaging, and enhancement pattern were analyzed. GRs were correlated with imaging features. The average GR of precursor lesions to >2 cm HCC was determined to be 0.23 cm/mo (standard deviation [SD], 0.32), with a doubling time of 5.26 months (SD, 5.44). The presence of increased signal intensity (SI) on T2-WI was associated with significantly higher growth (P = .0002), whereas increased intensity on T1-WI at the initial study was associated with a significantly lower GR (P = .0162). Furthermore, lesions with hypervascular enhancement with washout pattern had significantly higher GR (P = .0164). There is no evidence of differences in GRs seen in lesions with steatosis. Small precursor lesions with increased SI on T2-WI and a washout pattern of enhancement are associated with faster GRs, which may suggest more aggressive tumor biology. These features may be helpful in patient management and surveillance for HCC.


Transformation by polyoma virus is drastically reduced by substitution of phenylalanine for tyrosine at residue 315 of middle-sized tumor antigen.
We used an oligonucleotide to introduce an A----T transversion at nucleotide position 1178 in polyoma virus DNA. The single effect of this mutation is to substitute phenylalanine for tyrosine at residue 315 of the middle-sized tumor (mT) protein (antigen). This site was previously identified as a major phosphate acceptor in the protein kinase reaction of immunocomplexes containing mT antigen. Reconstituted polyoma virus with the transversion, Py-1178-T, produces an altered mT protein that shows about 20% of the activity of wild-type mT antigen in the immunocomplex kinase assay. This residual activity appears to be directed primarily at another tyrosine at position 322 in the mT protein. The transforming ability of Py-1178-T is drastically reduced compared to wild-type virus. The efficiency of transformation by the mutant is less than 1% of that of wild type in focus assays and less than 0.1% in soft-agar growth assays. Cells identified in focus assays with Py-1178-T are generally less transformed in their phenotype than wild-type transformed cells.


Age-Related Differences in Arm and Trunk Responses to First and Repeated Exposure to Laterally Induced Imbalances.
The objective of this study was to examine age-related differences in arm and trunk responses during first and repeated step induced balance perturbations. Young and older adults received 10 trials of unpredictable lateral platform translations. Outcomes included maximum arm and trunk displacement within 1 s of perturbation and at first foot lift off (FFLO), arm and neck muscle activity as recorded using electromyography (EMG), initial step type, balance confidence, and percentage of harness-assisted trials. Compared to young adults, older adults demonstrated greater arm and trunk angular displacements during the first trial, which were present at FFLO and negatively associated with balance confidence. Unlike young adults, recovery steps in older adults were directed towards the fall with a narrowed base of support. Over repeated trials, rapid habituation of first-trial responses of bilateral arm and trunk displacement and EMG amplitude was demonstrated in young adults, but was absent or limited in older adults. Older adults also relied more on harness assistance during balance recovery. Exaggerated arm and trunk responses to sudden lateral balance perturbations in older adults appear to influence step type and balance recovery. Associations of these persistently amplified movements with an increased reliance on harness assistance suggest that training to reduce these deficits could have positive effects in older adults with and without neurological disorders.


Integrated model for assessing the cost and CO2 emission (IMACC) for sustainable structural design in ready-mix concrete.
Cost has traditionally been considered the most important factor in the decision-making process. Recently, along with the consistent interest in environmental problems, environmental impact has also become a key factor. Accordingly, there is a need to develop a method that simultaneously reflects the cost and environmental impact in the decision-making process. This study proposed an integrated model for assessing the cost and CO(2) emission (IMACC) at the same time. IMACC is a model that assesses the cost and CO(2) emission of the various structural-design alternatives proposed in the structural-design process. To develop the IMACC, a standard on assessing the cost and CO(2) emission generated in the construction stage was proposed, along with the CO(2) emission factors in the structural materials, based on such materials' strengths. Moreover, using the economic and environmental scores that signify the cost and CO(2) emission reduction ratios, respectively, a method of selecting the best design alternative was proposed. To verify the applicability of IMACC, practical application was carried out. Structural designs were assessed, each of which used 21, 24, 27, and 30 MPa ready-mix concrete (RMC). The use of IMACC makes it easy to verify what the best design is. Results show the one that used 27 MPa RMC was the best design. Therefore, the proposed IMACC can be used as a tool for supporting the decision-making process in selecting the best design alternative.


Immunotoxin therapy of hematologic malignancies.
Patients with chemotherapy relapsed or refractory hematologic malignancies may be effectively treated with allogeneic or autologous stem cell transplants. However, many patients cannot be transplanted due to age, comorbidities, or lack of suitable donors. Further, a fraction of patients relapse post-transplant. Novel therapeutic agents that can kill multidrug-resistant malignant stem cells and are not myelosuppressive are needed. One class of such agents is immunotoxins. Immunotoxins consist of cell-selective ligands covalently linked to peptide toxins. The ligand delivers the molecule to specific cell surface receptors on malignant cells. The toxin triggers cell death either by reaching the cytosol and catalytically inactivating vital cell processes or by modifying the tumor cell surface membrane. We have synthesized immunotoxins for therapy of chemoresistant hematologic diseases. In this review, we will detail the synthesis of a number of these drugs and describe their preclinical and clinical activity. Several of these agents have shown dramatic antitumor effects in patients with hematologic neoplasms, and one immunotoxin has been approved for use by the US Food and Drug Administration (FDA). Over the next several decades, a growing number of these agents should reach the clinic.


Improving the classification of migraine subtypes: an empirical approach based on factor mixture models in the American Migraine Prevalence and Prevention (AMPP) Study.
Refine the classification of migraine subtypes by applying factor mixture models (FMM) to a large population sample of people with headache. Current classification of primary headache disorders is symptom-based and uses somewhat arbitrary boundaries developed by expert consensus. Symptom profiles and headache frequency are used to distinguish among probable migraine (PM), episodic migraine (EM), high-frequency episodic migraine (HFEM), and chronic migraine (CM). Herein, we used statistical approaches to parse the heterogeneity in the broad group of persons with migraine and test the hypothesis that the groups that emerge differ in prognosis. The American Migraine Prevalence and Prevention study mailed surveys to a sample of 120,000 US households selected to represent the US population in 2004. Follow-up surveys were sent to a random sample of 24,000 respondents with "severe headache" on an annual basis from 2005 to 2009. People meeting International Classification of Headache Disorders, Second Edition, criteria for migraine were classified as EM (<15 headache days/month) and CM (≥15 headache days/month) based on modified Silberstein-Lipton criteria. The EM group was subdivided into HFEM (10 to 14 headache days/month) and low-frequency episodic migraine (LFEM; <10 headache days/month). Factor mixture models (FMM) identified 5 subgroups of migraine (taxa) using data from the 2005 survey on the severity of migraine symptoms, average migraine pain intensity, headache-related disability, cutaneous allodynia and depression, as well as monthly headache and migraine frequency as determinants of class membership. We assessed the validity of these taxa by examining the distribution of clinical diagnoses at cross-section and the rate of CM onset within these groups. Data from the 2005 American Migraine Prevalence and Prevention survey were used for the FMM and data from the 2006-2009 surveys were used to assess prognosis of groups defined based on FMM. In total, 12,860 participants were eligible for classification analysis, including 10,162 with LFEM and 601 with HFEM, 1302 with probable migraine, and 795 with CM. Of these, 3152 (24.5%), 1076 (8.4%), 3896 (30.3%), 2251 (17.5%), and 2485 (19.3%) were assigned to Taxons 1, 2, 3, 4, and 5, respectively. Overall, there was a strong association between taxon assignment and clinical diagnosis. As the most prevalent disorder in the sample, EM was the largest contributor to each of the 5 taxa, constituting more than 80% of each group other than Taxon 2. Taxon 2 was enriched with the most severe spectrum of migraine including the highest concentrations of CM (28.4%) and HFEM (22.6%), whereas Taxon 5 represented the least severe end of the migraine spectrum including the lowest concentrations of CM (0%) and HFEM (0.08%). Validity of taxon assignment was tested by the ability of taxon membership to predict clinical course. For Taxon 2, 22% of those free of CM at baseline developed it. For Taxon 5, less than 2% of CM-free Taxon 5 members developed it. Statistically based classification using FMM extends traditional clinical syndrome-based diagnosis. FMM can serve as an important tool to parse phenotypic heterogeneity and identify natural migraine subgroups. This approach may improve our ability to diagnosis migraine, to select initial therapy, to predict prognosis, and to discover biomarkers and genes.


Association of Full Breastfeeding Duration with Postpartum Weight Retention in a Cohort of Predominantly Breastfeeding Women.
Full breastfeeding (FBF) is promoted as effective for losing pregnancy weight during the postpartum period. This study evaluated whether longer FBF is associated with lower maternal postpartum weight retention (PPWR) as compared to a shorter FBF duration. The MILK (Mothers and Infants Linked for Healthy Growth) study is an ongoing prospective cohort of 370 mother-infant dyads, all of whom fully breastfed their infants for at least 1 month. Breastfeeding status was subsequently self-reported by mothers at 3 and 6 months postpartum. Maternal PPWR was calculated as maternal weight measured at 1, 3, and 6 months postpartum minus maternal prepregnancy weight. Using linear mixed effects models, by 6 months postpartum, adjusted means ± standard errors for weight retention among mothers who fully breastfed for 1-3 (3.40 ± 1.16 kg), 3-6 (1.41 ± 0.69 kg), and ≥6 months (0.97 ± 0.32 kg) were estimated. Compared to mothers who reported FBF for 1-3 months, those who reported FBF for 3-6 months and ≥6 months both had lower PPWR over the period from 1 to 6 months postpartum (p = 0.04 and p < 0.01, respectively). However, PPWR from 3 to 6 months was not significantly different among those who reported FBF for 3-6 versus ≥6 months (p > 0.05). Interventions to promote FBF past 3 months may increase the likelihood of postpartum return to prepregnancy weight.


Sustained Clinical Efficacy and Mucosal Healing of Thiopurine Maintenance Treatment in Ulcerative Colitis: A Real-Life Study.
Thiopurines are commonly used for treating ulcerative colitis (UC), despite the fact that controlled evidence supporting their efficacy is limited. The aim of this study was to evaluate the long-term outcome of thiopurines as maintenance therapy in a large cohort of UC patients. All UC patients receiving thiopurine monotherapy at three tertiary IBD centers from 1995 to 2015 were identified. The primary endpoint was steroid-free clinical remission. Secondary endpoints were mucosal healing (MH), defined as Mayo endoscopic subscore 0, long-term safety, and predictors of sustained clinical remission. We identified 192 patients, contributing a total of 747 person-years of follow-up (median follow-up 36 months, range 1-210 months). Steroid dependency was the most common indication for thiopurine treatment (58%). Steroid-free remission occurred in 45.3% of patients; 36.3% stopped thiopurines because of treatment failure and 18.2% for adverse events or intolerance. The cumulative probability of maintaining steroid-free remission while on thiopurine treatment was 87%, 76%, 67.6%, and 53.4% at 12, 24, 36, and 60 months, respectively. MH occurred in 57.9% of patients after a median of 18 months (range 5-96). No independent predictors of sustained clinical remission could be identified. Thiopurines represent an effective and safe long-term maintenance therapy for UC patients.


Immunization against coccidiosis in pheasants with low-dose live sporulated oocysts of Eimeria colchici.
Low-dose immunization of pheasants with live Eimeria colchici oocysts was observed to be effective against massive challenge infection. Fourteen-day-old pheasants, in groups of 28, were orally inoculated with about 100, 250, 500, 1000 and 2000 sporulated oocysts. These birds were then challenged homologously with about 120 000 sporulated oocysts 18 days after the immunization. During the 12-day observation period after the challenge infection, over 92% of the immunized pheasants were still alive, but only 11% of the non-immunized control birds survived the challenge infection. Moreover, the number of oocysts produced after challenge infection of the immunized group was only 10 to 19% of the positive non-immunized control group. The crowding effect of E. colchici infection in pheasant was thought to occur based on the significant difference of the relationship between inoculation doses, daily oocysts excretion and the amount of the faeces discharged, as analyzed by Pearson correlation analysis. Our results showed that immunization of pheasants with a low dose of E. colchici oocysts is feasible to help protect the birds from massive homologous infection, which can be fatal.


Evaluation of type-B RR dimerization in poplar: A mechanism to preserve signaling specificity?
Plants possess specific signaling pathways, such as the MultiStep Phosphorelay (MSP), which is involved in cytokinin and ethylene sensing, and light, drought or osmotic stress sensing. These MSP comprise histidine-aspartate kinases (HKs) as receptors, histidine phosphotransfer (HPts) proteins acting as phosphorelay proteins, and response regulators (RRs), some of which act as transcription factors (type-B RRs). In previous studies, we identified partners of the poplar osmosensing signaling pathway, composed of two HKs, three main HPts, and six type-B RRs. To date, it is unresolved as to how cytokinin or osmotic stress signal specificity is achieved in the MSP in order to generate specific responses. Here, we present a large-scale interaction study of poplar type-B RR dimerization. Using the two-hybrid assay, we were able to show the homodimerization of type-B RRs, the heterodimerization of duplicated type-B RRs, and surprisingly, a lack of interaction between some type-B RRs belonging to different duplicates. The lack of interaction of the duplicates RR12-14 and RR18-19, which are involved in the osmosensing pathway has been confirmed by BiFC experiments. This study reveals, for the first time, an overview of type-B RR dimerization in poplar and makes way for the hypothesis that signal specificity for cytokinin or osmotic stress could be in part due to the fact that it is impossible for specific type-B RRs to heterodimerize.


Organisation and quality monitoring for point-of-care testing (POCT) in Belgium: proposal for an expansion of the legal framework for POCT into primary health care.
There is a trend towards decentralisation of laboratory tests by means of Point-of-Care testing (POCT). Within hospitals, Belgian law requires a POCT policy, coordinated by the clinical laboratory. There is however no legal framework for POCT performed outside the hospital: no reimbursement, no compulsory quality monitoring and no limits nor control on the prices charged to the patient. Uncontrolled use of POCT can have negative consequences for individual and public health. We propose that POCT outside hospitals would only be reimbursed for tests carried out within a legal framework, requiring evidence-based testing and collaboration with a clinical laboratory, because clinical laboratories have procedures for test validation and quality monitoring, are equipped for electronic data transfer, are familiar with logistical processes, can provide support when technical issues arise and can organise and certify training. Under these conditions the government investment will be offset by health benefits, e.g. fall in antibiotic consumption with POCT for CRP in primary care, quick response to SARS-CoV2-positive cases in COVID-19 triage centres. 1° extension of the Belgian decree on certification of clinical laboratories to decentralised tests in primary care; 2° introduction of a separate reimbursement category for POCT; 3° introduction of reimbursement for a limited number of specified POCT; 4° setup of a Multidisciplinary POCT Advisory Council, the purpose of which is to draw up a model for reimbursement of POCT, to select tests eligible for reimbursement and to make proposals to the National Institute for Health and Disability Insurance (RIZIV/INAMI).


Nanoscale electron transport at the surface of a topological insulator.
The use of three-dimensional topological insulators for disruptive technologies critically depends on the dissipationless transport of electrons at the surface, because of the suppression of backscattering at defects. However, in real devices, defects are unavoidable and scattering at angles other than 180° is allowed for such materials. Until now, this has been studied indirectly by bulk measurements and by the analysis of the local density of states in close vicinity to defect sites. Here, we directly measure the nanoscale voltage drop caused by the scattering at step edges, which occurs if a lateral current flows along a three-dimensional topological insulator. The experiments were performed using scanning tunnelling potentiometry for thin Bi2Se3 films. So far, the observed voltage drops are small because of large contributions of the bulk to the electronic transport. However, for the use of ideal topological insulating thin films in devices, these contributions would play a significant role.


Regular physical exercise improves physical motor functions and biochemical markers in middle-age and elderly women.
Lifestyle-related diseases among middle-age and elderly people have become serious problems. Underlying causes might be related to the changes in the lifestyle including the absence of regular physical exercise. To clarify the significance of regular physical exercise to prevent lifestyle-related diseases, we studied motor functions and blood chemistry examinations in middle-age and elderly women (over 40 years old) who performed regular physical exercise for 2 years (exercise group) and those who initially did not (control group). In study 1, VO2max significantly increased in the exercise group compared with the control group in the under 60 years old groups. In the over 60 years old groups, VO2max, foot balance, and HDL cholesterol significantly increased. Plasma glucose at 120 minutes after the 75 g oral glucose tolerance test, fasting insulin, homeostasis model assessment (HOMA-R), and high sensitivity C-reactive protein (hsCRP) significantly decreased in the exercise group compared with the control group. In study 2, a 1-year exercise program significantly improved physical functions and biochemical markers in the control group. These results suggest that regular physical exercise might help to maintain sound motor functions and decrease insulin resistance and a risk for arteriosclerosis.


Outcomes after nonemergent electrical cardioversion for atrial arrhythmias.
Electrical cardioversion (ECV) is recommended for rhythm control in patients with atrial arrhythmia; yet, ECV use and outcomes in contemporary practice are unknown. We reviewed all nonemergent ECVs for atrial arrhythmias at a tertiary care center (2010 to 2013), stratifying patients by transesophageal echocardiography (TEE) use before ECV and comparing demographics, history, vitals, and laboratory studies. Outcomes included postprocedural success and complications and repeat cardioversion, rehospitalization, and death within 30 days. Overall, 1,017 patients underwent ECV, 760 (75%) for atrial fibrillation and 240 (24%) for atrial flutter; 633 underwent TEE before ECV and 384 did not. TEE recipients were more likely to be inpatients (74% vs 44%, p <0.001), have higher mean CHADS2 scores (2.6 vs 2.4, p = 0.03), and lower mean international normalized ratios (1.2 vs 2.1, p <0.001). Overall, 89 patients (8.8%) did not achieve sinus rhythm and 14 experienced procedural complications (1.4%). Within 30 days, 80 patients (7.9%) underwent repeat ECV, 113 (11%) were rehospitalized, and 14 (1.4%) died. Although ECV success was more common in patients who underwent TEE before ECV (77% vs 68%, p = 0.01), there were no differences in 30-day death or rehospitalization rates (11.1% vs 13.0%, p = 0.37). In multivariate analyses, higher pre-ECV heart rate was associated with increased rehospitalization or death (adjusted hazard ratio 1.15/10 beats/min, 95% confidence interval 1.07 to 1.24, p <0.001), whereas TEE use was associated with lower rates (adjusted hazard ratio 0.58, 95% confidence interval 0.39 to 0.86, p = 0.007). In conclusion, failures, complications, and rehospitalization after nonemergent ECV are common and associated more with patient condition than procedural characteristics. TEE use was associated with better clinical outcomes.


A novel industrial-scale strategy to prevent degradation and caking of ammonium nitrate.
Several research studies have been performed to minimise the hygroscopicity of ammonium nitrate for increasing its commercial value and decreasing the nitrogen content. In this study, the hygroscopicity of ammonium nitrate was reduced using silicic acid, calcium lignosulfonate, and sodium silicate in the two-stage vacuum ammonium nitrate production process. Degradation of ammonium nitrate was observed after two years of storage, which is considered a standard by the European Fertilizer Manufacturers Association.


Benefit cost scenarios of potential oral rabies vaccination for skunks in California.
Scenario-based analyses were computed for benefits and costs linked with hypothetical oral rabies vaccination (ORV) campaigns to contain or eliminate skunk-variant rabies in skunks (Mephitis mephitis) in California, USA. Scenario 1 assumed baiting eight zones (43,388 km(2) total) that comprised 73% of known skunk rabies locations in the state. Scenario 2 also assumed baiting these eight zones, but further assumed that added benefits would result from preventing the spread of skunk-variant rabies into Los Angeles County, USA. Scenarios assumed a fixed bait cost ($1.24 each) but varied campaigns (one, two and three annual ORV applications), densities of baits (37.5/km(2), 75/km(2) and 150/km(2)), levels of prevention (50%, 75%, and 100%), and contingency expenditures if rabies recurred (20%, 40%, and 60% of campaign costs). Prorating potential annual benefits during a 12-yr time horizon yielded benefit-cost ratios (BCRs) between 0.16 and 2.91 and between 0.34 and 6.35 for Scenarios 1 and 2, respectively. Economic issues relevant to potentially managing skunk-variant rabies with ORV are discussed.


Human blood-based anti-inflammatory solution inhibits osteoarthritis progression in a meniscal-tear rat study.
Current osteoarthritis (OA) research searches for treatments that modify the course of disease progression. Autologous Protein Solution (APS) is derived from whole blood and is a unique autologous therapy that contains high concentrations of white blood cells, platelets, and concentrated plasma, providing cytokines that can target the underlying mechanisms of disease progression. The APS Kit is currently under investigation for clinical use in the USA (NCT02262364). The aim of this study was to determine if APS has disease-modifying properties in the well-characterized rat meniscal tear-induced model of OA. Thirty male athymic rats underwent surgery to induce OA by a complete tear of the medial meniscus of the right knee. Seven days later, rats were administered 50 μl intra-articular (IA) APS from a human donor or phosphate buffered saline (PBS) control. Rats were euthanized 3 weeks following treatment and knee joints were processed for histological analysis. Collagen and cartilage degeneration were decreased by APS treatment, resulting in a significantly improved total joint score in APS-treated rats compared to those treated with the PBS control. No significant variations in gait analysis, weight gain, osteophyte score, or synovitis score were observed between APS- and PBS-treated animals. There were no adverse effects of APS reported in the study. Treatment with a single IA injection of APS reduced the cartilage degeneration that characterizes the progression of OA. Further studies are necessary to determine if APS can modify OA disease progression in humans. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2260-2268, 2017.


Evolutionary Patterns of Modularity in the Linkage Systems of the Skull in Wrasses and Parrotfish.
The concept of modularity is fundamental to understanding the evolvability of morphological structures and is considered a central framework for the exploration of functionally and developmentally related subsets of anatomical traits. In this study, we explored evolutionary patterns of modularity and integration in the 4-bar linkage biomechanical system of the skull in the fish family Labridae (wrasses and parrotfish). We measured evolutionary modularity and rates of shape diversification of the skull partitions of three biomechanical 4-bar linkage systems using 205 species of wrasses (family: Labridae) and a three-dimensional geometric morphometrics data set of 200 coordinates. We found support for a two-module hypothesis on the family level that identifies the bones associated with the three linkages as being a module independent from a module formed by the remainder of the skull (neurocranium, nasals, premaxilla, and pharyngeal jaws). We tested the patterns of skull modularity for four tribes in wrasses: hypsigenyines, julidines, cheilines, and scarines. The hypsigenyine and julidine groups showed the same two-module hypothesis for Labridae, whereas cheilines supported a four-module hypothesis with the three linkages as independent modules relative to the remainder of the skull. Scarines showed increased modularization of skull elements, where each bone is its own module. Diversification rates of modules show that linkage modules have evolved at a faster net rate of shape change than the remainder of the skull, with cheilines and scarines exhibiting the highest rate of evolutionary shape change. We developed a metric of linkage planarity and found the oral jaw linkage system to exhibit high planarity, while the rest position of the hyoid linkage system exhibited increased three dimensionality. This study shows a strong link between phenotypic evolution and biomechanical systems, with modularity influencing rates of shape change in the evolution of the wrasse skull.


Impact of Undergoing Thoracolumbar Surgery on Patient Psychosocial Profiles.
Prospective cohort study. Investigate the impact of thoracolumbar surgery on patients' psychosocial profiles. A prospective cohort study of thoracolumbar surgery patients (N = 177). Measures of interest collected at baseline and 24-months after surgery were: modified Oswestry Disability Index (mODI), Numerical Rating Scores for Back Pain (NRS-B), Leg Pain (NRS-L), Pain Catastrophizing Scale (PCS), Tampa Scale of Kinesiophobia (TSK), Chronic Pain Acceptance Questionnaire-8 (CPAQ-8), Multidimensional Scale of Perceived Social Support (MSPSS), Mental Component Summary (MCS) and patient expectations for surgery impacts on mental well-being. Cohorts were separated based on attaining meaningful change defined as either 30% improvement or minimal scores in NRS-B, NRS-L and mODI. Mixed measures ANOVAs were run (α = .05). Patients who showed meaningful change had significant improvements in PCS, TSK and CPAQ-8 scores but not in MSPSS scores. Patients had improvement in MCS scores over 24-months follow-up, but this change was not significantly different based on attainment of meaningful change. Overall, 75.9% of patients reported their mental well-being expectations were met. Patients who did not achieve meaningful change showed no change on any psychosocial measures with only 55.9% reporting their mental well-being expectations met. Thoracolumbar surgery results in significant improvement of psychosocial variables for patients who experienced meaningful change for pain and disability. Worsening of psychosocial health was not evident in patients who did not attain meaningful change.


[The concomitant use of radiotherapy and chemotherapy for the treatment of solid malignant tumors].
Various clinical trials carried out during the last few decades have clearly demonstrated that the concomitant use of radiotherapy and chemotherapy significantly improves local control in a variety of advanced solid tumours. In most of these trials where an improvement was noted, cisplatin was used in addition to radiotherapy either on its own or in combination with other cytostatics. This has led to improved survival rates in head and neck, lung and cervical cancer. For these solid tumours, the interaction of radiotherapy with chemotherapy appears to be schedule dependent, as no such an improvement was observed if chemotherapy was given prior to or after radiotherapy. A major advantage of this combined therapy is that a structure-preserving treatment for patients with advanced larynx or anal cancer is more often possible. Major further improvement can be expected from the design and use of new drugs that influence the pathways leading to cell death after irradiation.


Sector-wide approaches (SWAps) in health: what have we learned?
Sector-wide approaches (SWAps) in health were developed in the early 1990s in response to widespread dissatisfaction with fragmented donor-sponsored projects and prescriptive adjustment lending. SWAps were intended to provide a more coherent way to articulate and manage government-led sectoral policies and expenditure frameworks and build local institutional capacity as well as offer a means to more effective relationships between governments and donor agencies. The global health landscape has changed dramatically since then. Although many countries have undertaken SWAps, the experience deviated considerably from the early vision, and many of the problems in national health systems persist. SWAps have contributed to the development of robust national health policies and transparent expenditure frameworks as well as strengthening institutional capacity, though the levels of success vary widely. Government stewardship of donors and local stakeholders as well as their political will to implement health strategies also vary highly. Although SWAps are geared towards consensus building policy changes at the national level, in the face of urgent global health concerns, notably the HIV epidemic, donors often by-passed SWAp arrangements through global health initiatives intended to address international priorities. Yet, a key to sustaining global health initiatives is how well they can be integrated into national health systems, a task requiring a return to SWAp principles. Despite shortcomings, SWAps have remained a popular approach for supporting alignment, harmonization and improved accountability between donors and country governments, increasing predictability of aid and reducing fragmentation. The future of SWAps will depend on stronger government oversight and innovative institutional arrangements to support health strategies that address the need for both targeted initiatives and stronger health systems to provide a wide range of public health and clinical services. For development assistance to be more effective, it will also depend on better discipline by donors to support national governments through transparent negotiation.


Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-binding repertoires of common HLA molecules.
An HLA-A3-like supertype (minimally comprised of products from the HLA class I alleles A3, A11, A31, A*3301, and A*6801) has been defined on the basis of (a) structural similarities in the antigen-binding groove, (b) shared main anchor peptide-binding motifs, (c) the identification of peptides cross-reacting with most or all of these molecules, and (d) the definition of an A3-like supermotif that efficiently predicts highly cross-reactive peptides. Detailed secondary anchor maps for A3, A11, A31, A*3301, and A*6801 are also described. The biologic relevance of the A3-like supertype is indicated by the fact that high frequencies of the A3-like supertype alleles are conserved in all major ethnic groups. Because A3-like supertype alleles are found in most major HLA evolutionary lineages, possibly a reflection of common ancestry, the A3-like supermotif might in fact represent a primeval human HLA class I peptide-binding specificity. It is also possible that these phenomena might be related to optimal exploitation of the peptide specificity by human TAP molecules. The grouping of HLA alleles into supertypes on the basis of their overlapping peptide-binding repertoires represents an alternative to serologic or phylogenetic classification.


The handedness and origin of supernumerary limb structures following 180 degrees rotation of the chick wing bud on its stump.
The pattern of differentiated wing structures formed following 180 degrees rotation of the undifferentiated wing bud tip on its base was examined in detail. These analyses were performed to determine the handedness and origin of the supernumerary structures which arise. In contrast to the variable classes of symmetric and/or asymmetric limb anatomies observed following the same operation with amphibian regeneration blastemas, wings of predictable handedness were observed. Both the graft and stump contributed cells to the supernumerary structures. These results are discussed in the light of two current models describing the developing chick limb and analysed diagrammatically within the framework of one of these models, the polar coordinate model.


Harmful postures and musculoskeletal symptoms among fish trimmers of a fish processing factory in ghana: a preliminary investigation.
This study investigated musculoskeletal symptoms among fish trimmers (skinners and polishers) in a fish processing factory in Ghana. The methods used included administration of questionnaire, walk through observation, interview, task analysis and future workshop. All 50 female participants answered and submitted their questionnaires. Of the 11 operations performed by skinners only 1 was rated as low risk. Also of the 12 operations performed by polishers only 2 were rated as low risk. Neck side bending, neck flexion, prolonged standing, shoulder elevation, abducted arms, repetitious reaching forward and wrist deviation were observed in most operations. This corresponds with questionnaire results in which musculoskeletal symptoms were mostly prevalent in the neck, the shoulder, the low back, the wrist/hand and the knee regions. There was no significant correlation (p < .05) between musculoskeletal symptoms and age, working hours and length of service. Task redesign, workplace changes and worker training were suggested to improve the work.


Increased intracellular localization of brain GLUT-1 transporter in response to ethanol during chick embryogenesis.
Fetal exposure to ethanol is associated with growth retardation of the developing central nervous system. We have previously described a chick model to study the molecular mechanism of ethanol effects on glucose metabolism in ovo. Total membrane fractions were prepared from day 4, day 5, and day 7 chick embryos exposed in ovo to ethanol or to vehicle. By Western blotting analysis, ethanol exposure caused a mean 7- to 10-fold increase in total GLUT-1 and a 2-fold increase in total GLUT-3. However, glucose uptake by ethanol-treated cells increased by only 10%. Analysis of isolated plasma (PM) and intracellular (IM) membranes from day 5 cranial tissue revealed a mean 25% decrease in GLUT-1 in the PM and a 66% increase in the IM in the ethanol group vs. control. The amount of PM GLUT-3 was unchanged but that of IM GLUT-3 was significantly decreased. The data suggest that GLUT-3 cell surface expression may be resistant to the suppressive effects of ethanol in the developing brain of ethanol-treated embryos. The overall increase in GLUT-1 may reflect a deregulation of the transporter induced by ethanol exposure. The increased IM localization and decreased amount of PM GLUT-1 may be a mechanism used by the ethanol-treated cell to maintain normal glucose uptake despite the overall increased level of the transporter.


Diabetes at work: a grounded-theory pilot study.
Diabetes at Work is a qualitative grounded-theory pilot study designed to examine the factors impacting older adults' experience managing diabetes in the workplace and maintaining gainful employment. Six working adults, 55 years and older, with Type 2 diabetes were interviewed from a symbolic interactionist perspective using grounded-theory methodology. Categories that arose from this study included minimalization, fearing the future, and taking up diabetes self-management at work. The results provide insight for occupational health nurses about the issues faced by older workers with chronic disease, a starting point for planning future interventions with this potentially vulnerable population.


Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.
The association of triglycerides with incident cardiovascular disease remains controversial. Although triglyceride levels are typically obtained in the fasting state, postprandial hypertriglyceridemia may play an important role in atherosclerosis. To determine the association of triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events. Prospective study of 26,509 initially healthy US women (20,118 fasting and 6391 nonfasting) participating in the Women's Health Study, enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years. Triglyceride levels were measured in blood samples obtained at time of enrollment. Hazard ratios for incident cardiovascular events (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death). At baseline, triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance. During a median follow-up of 11.4 years, 1001 participants experienced an incident cardiovascular event (including 276 nonfatal myocardial infarctions, 265 ischemic strokes, 628 coronary revascularizations, and 163 cardiovascular deaths), for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up. After adjusting for age, blood pressure, smoking, and use of hormone therapy, both fasting and nonfasting triglyceride levels predicted cardiovascular events. Among fasting participants, further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association (fully adjusted hazard ratio [95% confidence interval] for increasing tertiles of triglyceride levels: 1 [reference], 1.21 [0.96-1.52], and 1.09 [0.85-1.41] [P = .90 for trend]). In contrast, nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models (hazard ratio [95% confidence interval] for increasing tertiles of levels: 1 [reference], 1.44 [0.90-2.29], and 1.98 [1.21-3.25] [P = .006 for trend]). In secondary analyses stratified by time since participants' last meal, triglyceride levels measured 2 to 4 hours postprandially had the strongest association with cardiovascular events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P<.001 for trend]), and this association progressively decreased with longer periods of fasting. In this cohort of initially healthy women, nonfasting triglyceride levels were associated with incident cardiovascular events, independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels showed little independent relationship.


Pediatric renal transplantation in syria: a single center experience.
Renal transplantation (RTx) is widely accepted as the preferred method of treatment for children with end-stage renal disease (ESRD). This is a retrospective analysis of the results of RTx in children performed at the Surgical Kidney Hospital, Damascus, Syria. Between November 2002 and November 2004, a total of 176 RTx procedures have been performed in our center. Of them, 11 recipients (6%) were younger than 14 years of age. The mean age was 11 years with range of 5 to 14 years. There were six males (55%) and five females (45%). All patients received kidneys from living donors. Seven donors were related (64 %) while four (36%) were unrelated .The cause of ESRD in these patients were reflux nephropathy in three, nephronophthisis and hypoplastic kidneys in two cases each and polycystic kidney disease, rapidly progressive crescentic glomerulonephritis, Alport's syndrome and chronic pyelonephritis in one patient each. All grafts were placed extra-peritoneally. Immunosuppression was based on triple therapy with cyclosporine (CsA) mycophenolate mofetil (MMF), and prednisolone. Tacrolimus (TAC), MMF, and prednisolone, and sirolimus (SRL), MMF, and prednisolone were used in one patient each. Induction immunosuppression in immunologically high-risk patients was, with anti-thymocyte globulin (ATG) in one patient and basiliximab in two patients. The mean duration of follow-up was 12 months {3 to 24 months}. All 11 (100 %) patients were alive at last follow-up with functioning graft. Ten patients (88%) had normal graft function and one (12%) had mild graft dysfunction. Complications encountered were infections in four patients, early steroid-responsive acute rejection in one patient, and mild biopsy-proven chronic rejection in another patient; the latter probably due to poor compliance. No urological complications were encountered. Our study, despite involving a small number of patients with a relatively short duration of follow-up, suggests that the results of pediatric renal transplant at our center are encouraging.


Direct observation and modelling of ordered hydrogen adsorption and catalyzed ortho-para conversion on ETS-10 titanosilicate material.
Hydrogen physisorption on porous high surface materials is investigated for the purpose of hydrogen storage and hydrogen separation, because of its simplicity and intrinsic reversibility. For these purposes, the understanding of the binding of dihydrogen to materials, of the structure of the adsorbed phase and of the ortho-para conversion during thermal and pressure cycles are crucial for the development of new hydrogen adsorbents. We report the direct observation by IR spectroscopic methods of structured hydrogen adsorption on a porous titanosilicate (ETS-10), with resolution of the kinetics of the ortho-para transition, and an interpretation of the structure of the adsorbed phase based on classical atomistic simulations. Distinct infrared signals of o- and p-H2 in different adsorbed states are measured, and the conversion of o- to p-H2 is monitored over a timescale of hours, indicating the presence of a catalyzed reaction. Hydrogen adsorption occurs in three different regimes characterized by well separated IR manifestations: at low pressures ordered 1:1 adducts with Na and K ions exposed in the channels of the material are formed, which gradually convert into ordered 2:1 adducts. Further addition of H2 occurs only through the formation of a disordered condensed phase. The binding enthalpy of the Na+-H2 1:1 adduct is of -8.7+/-0.1 kJ mol(-1), as measured spectroscopically. Modeling of the weak interaction of H2 with the materials requires an accurate force field with a precise description of both dispersion and electrostatics. A novel three body force field for molecular hydrogen is presented, based on the fitting of an accurate PES for the H2-H2 interaction to the experimental dipole polarizability and quadrupole moment. Molecular mechanics simulations of hydrogen adsorption at different coverages confirm the three regimes of adsorption and the structure of the adsorbed phase.


Nanostructured metal oxide gas sensors, a survey of applications carried out at SENSOR lab, Brescia (Italy) in the security and food quality fields.
In this work we report on metal oxide (MOX) based gas sensors, presenting the work done at the SENSOR laboratory of the CNR-IDASC and University of Brescia, Italy since the 80s up to the latest results achieved in recent times. In particular we report the strategies followed at SENSOR during these 30 years to increase the performance of MOX sensors through the development of different preparation techniques, from Rheotaxial Growth Thermal Oxidation (RGTO) to nanowire technology to address sensitivity and stability, and the development of electronic nose systems and pattern recognition techniques to address selectivity. We will show the obtained achievement in the context of selected applications such as safety and security and food quality control.


Pure human hematopoietic progenitors: direct inhibitory effect of transforming growth factors-beta 1 and -beta 2.
TGF-beta 1 and TGF-beta 2 are effective inhibitors of hematopoiesis. We report that colony formation by pure peripheral blood CD34+CD33- BFU-E and CFU-GM (100 cells/dish) is effectively inhibited by both molecules, although TGF-beta 1 is up to 10-fold more potent than TGF-beta 2. Therefore, the effect of these molecules is apparently direct, rather than mediated by accessory cells. The maximal inhibitory activity of TGF-beta is exerted essentially at the early progenitor level, whereas BFU-E/CFU-GM primed for 48 h and IL-3, GM-CSF, and erythropoietin become insensitive to its action. In addition, [3H]TdR suicide experiments indicate that TGF-beta 2 blocks the IL-3-induced progression of early progenitors into the S phase of the cell cycle, whereas IL-6 and bFGF potentiate their entry into the mitotic process. Altogether, these results are compatible with the hypothesis that TGF-beta plays a relevant regulatory role in the homeostasis of early hematopoietic proliferation/differentiation.


Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.
To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively. We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.


Gain-of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease.
Isolated cardiac conduction block is a relatively common condition in young and elderly populations. Genetic predisposing factors have long been suspected because of numerous familial case reports. Deciphering genetic predisposing factors of conduction blocks may give a hint at stratifying conduction block carriers in a more efficient way. One Lebanese family and 2 French families with autosomal dominant isolated cardiac conduction blocks were used for linkage analysis. A maximum combined multipoint lod score of 10.5 was obtained on a genomic interval including more than 300 genes. After screening 12 genes of this interval for mutation, we found a heterozygous missense mutation of the TRPM4 gene in each family (p.Arg164Trp, p.Ala432Thr, and p.Gly844Asp). This gene encodes the TRPM4 channel, a calcium-activated nonselective cation channel of the transient receptor potential melastatin (TRPM) ion channel family. All 3 mutations result in an increased current density. This gain of function is due to an elevated TRPM4 channel density at the cell surface secondary to impaired endocytosis and deregulation of Small Ubiquitin MOdifier conjugation (SUMOylation). Furthermore, we showed by immunohistochemistry that TRPM4 channel signal level is higher in atrial cardiomyocytes than in common ventricular cells, but is highest in Purkinje fibers. Small bundles of highly TRPM4-positive cells were found in the subendocardium and in rare intramural bundles. the TRPM4 gene is a causative gene in isolated cardiac conduction disease with mutations resulting in a gain of function and TRPM4 channel being highly expressed in cardiac Purkinje fibers.