Effect of root morphology on the susceptibility of endodontically treated teeth to vertical root fracture: An ex-vivo model.
Vertical root fracture (VRF) of endodontically treated teeth is relatively common, and the involved teeth have a poor prognosis. Previous destructive methodologies applied force to the root in an uneven manner; thus, the associated experiments could not truly assess the mechanical behavior of VRF. This problem was resolved in the current study via the novel application of a bursting pressure methodology to endodontically treated maxillary central incisors and premolars. Hydrostatic pressure was applied inside the root canal through a cannula bonded to the coronal access cavity, and the apical foramen was sealed. VRFs were observed as water burst from the fractured root surface. Morphometric parameters were measured by staining and serially sectioning the roots. The bursting pressure was significantly lower in the premolars compared with that in the incisors (19.1±3.3MPa and 25.5. ±4.5MPa, respectively, p=0.001). Cracks in the roots appeared from the apex to the cement enamel junction (CEJ) (61%), apex to mid-root (26%) and mid-root to CEJ (13%), and they involved either two root surfaces (52%) or one root surface (48%) and closely resembled clinical VRF cases. Positive correlations were found between the bursting pressure and the proximal root wall thickness, whereas correlations were not observed between the bursting pressure and the buccal or lingual wall thicknesses. Statistical Analyses of Covariance (ANCOVA) models showed that the proximal wall thickness and an elliptically shaped root cross section were the variables that indicated the differences in strength between premolars, which are more prone to VRF, and maxillary central incisors, which are less prone to VRF.


Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses.
"Day-7" myeloid DCs are commonly used in the clinic. However, there is a strong need to develop DCs faster that have the same potent immunostimulatory capacity as "Day-7" myeloid DCs and at the same time minimizing time, labor and cost of DC preparations. Although "2 days" DCs can elicit peptide-specific responses, they have not been demonstrated to engulf, process and present complex whole tumor lysates, which could be more convenient and personalized source of tumor antigens than defined peptides. In this preclinical study, we evaluated the T-cell stimulatory capacity of Day-2, Day-4, and Day-7 cultured monocyte-derived DCs loaded with SKOV3 cell whole lysate prepared by freeze-thaw or by UVB-irradiation followed by freeze-thaw, and matured with lipopolysaccharide (LPS) and interferon (IFN)-gamma. DCs were evaluated for antigen uptake, and following maturation with LPS and IFN-gamma, DCs were assessed for expression of CD80, CD40, CD86, ICAM-1 and CCR7, production of IL-12p70 and IP-10, and induction of tumor-specific T-cell responses. Day-4 and Day-7 DCs exhibited similar phagocytic abilities, which were superior to Day-2 DCs. Mature Day-7 DCs expressed the highest CD40 and ICAM-1, but mature Day-4 DCs produced the most IL-12p70 and IP-10. Importantly, Day-4 and Day-7 DCs derived from ovarian cancer patients stimulated equally strongly tumor-specific T-cell responses. This is the first study demonstrating the highly immunogenic and strong T-cell stimulatory properties of Day-4 myeloid DCs, and provided important preclinical data for rapid development of potent whole tumor lysate-loaded DC vaccines that are applicable to many tumor types.


Temporal changes of noninvasive electrocardiographic risk factors for sudden cardiac death in post-myocardial infarction patients with preserved ejection fraction: Insights from the PRESERVE-EF study.
Several noninvasive risk factors (NIRFs) have been proposed for sudden cardiac death risk stratification in post-myocardial infarction (post-MI) patients with preserved ejection fraction (EF). However, it remains unclear if these factors change over time. We evaluated seven electrocardiographic NIRFs as they were described in the PRESERVE-EF trial in 80 post-MI patients with EF ≥ 40%, at least 40 days after revascularization and 1 year later. Mean patient age was 56 ± 10 years, and 88% were men. Mean EF was 50 ± 5%. The prevalence of (a) positive late potentials (27.5% vs. 28.8%, p = .860), (b) >30 premature ventricular complexes/hour (8.8% vs. 11.3%, p = .598), (c) nonsustained ventricular tachycardia (8.8% vs. 5%, p = .349), (d) standard deviation of normal RR intervals <75 ms (3.8% vs. 3.8%, p = 1.000), (e) QTc derived from 24-hr electrocardiography >440 ms (men) or >450 ms (women) (17.5% vs. 17.5%, p = 1.000), (f) deceleration capacity ≤4.5 ms and heart rate turbulence onset ≥0% and slope ≤2.5 ms (2.5% vs. 3.8%. p = 1.000), and (g) ambulatory T-wave alternans ≥65 μV in two Holter channels (6.3% vs. 6.3%, p = 1.000) were similar between the two measurements. However, five patients (6.3%) without any NIRFs during the first assessment had at least one positive NIRF at the second assessment and six patients (7.5%) with at least one NIRF at baseline had no positive NIRFs at 1 year. While the prevalence of the examined electrocardiographic NIRFs between the two examinations was similar on a population basis, some patients without NIRFs at baseline developed NIRFs at 1 year and vice versa, highlighting the need for risk factor reassessment during follow-up.


Sensitivity to ischaemia of single sympathetic nerve fibres innervating the dorsum of the human foot.
Changes in nerve conduction velocity following an impulse (i.e. velocity recovery cycles) reflect after-potentials, and can provide an indication of altered nerve membrane properties. This study used microneurography to assess the effects of ischaemia on single human sympathetic fibres innervating the dorsum of the foot. It was found that velocity recovery cycles can distinguish whether a sympathetic nerve fibre is depolarized or not. The method may be used to detect membrane depolarization of sympathetic nerve fibres in human patients when autonomic neuropathy is suspected. The aim of this study was to determine whether velocity recovery cycles (VRCs) could detect the effects of ischaemia on sympathetic nerve fibres. VRCs of human sympathetic nerve fibres of the superficial peroneal nerve innervating the dorsum of the foot were recorded by microneurography in seven healthy volunteers. Sympathetic nerve fibres were identified by studying their response to manoeuvres increasing sympathetic outflow and by measuring activity-dependent slowing at 2 Hz stimulation. VRCs were assessed at rest, during 30 min of induced limb ischaemia and during 20 min of recovery after ischaemia. From each VRC was measured the relative refractory period (RRP), the supernormality and the time to peak supernormality (SN@). During ischaemia, RRP increased from the baseline value of 37.4 ± 8.7 ms (mean ± SEM) to 67.1 ± 12.1 ms (P < 0.01) and SN@ increased from 68.6 ± 9.8 ms to 133.8 ± 11.0 ms (P < 0.005). The difference between SN@ and RRP separated ischaemic from non-ischaemic sympathetic nerve fibres. It is concluded that these sympathetic nerve fibres are sensitive to ischaemia, and that VRCs provide a method to study changes of axonal membrane potential of human sympathetic nerve fibres in vivo.


Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey.
Co-morbidities frequently accompany heart failure (HF), contributing to increased morbidity and mortality, and an impairment of quality of life. We assessed the prevalence, determinants, regional variation, and prognostic implications of co-morbidities in patients with chronic HF in Europe. A total of 3226 European outpatients with chronic HF were included in this analysis of the European Society of Cardiology (ESC) Heart Failure Pilot Survey. The following co-morbidities were considered: diabetes, hyper- and hypothyroidism, stroke, COPD, sleep apnoea, chronic kidney disease (CKD), and anaemia. Prognostic implications of co-morbidities were evaluated using population attributable risks (PARs), and patients were divided into geographic regions. Clinical endpoints were all-cause mortality and HF hospitalization. The majority of patients (74%) had a least one co-morbidity, the most prevalent being CKD (41%), anaemia (29%), and diabetes (29%). Co-morbidities were independently associated with higher age (P < 0.001), higher NYHA functional class (P < 0.001), ischaemic aetiology of HF (P < 0.001), higher heart rate (P = 0.011), history of hypertension (P < 0.001), and AF (P < 0.001). Only diabetes, CKD, and anaemia were independently associated with a higher risk of mortality and/or HF hospitalization. There were marked regional differences in prevalence and prognostic implications of co-morbidities. Prognostic implications of co-morbidities (PARs) were: CKD = 41%, anaemia = 37%, diabetes = 14%, COPD = 10%, and <10% for all other co-morbidities. In this pilot survey, co-morbidities are prevalent in patients with chronic HF and are related to the severity of the disease. The presence of diabetes, CKD, and anaemia was independently related to increased mortality and HF hospitalization, with the highest PAR for CKD and anaemia.


Rate of decline in serum PFOA concentrations after granular activated carbon filtration at two public water systems in Ohio and West Virginia.
Drinking water in multiple water districts in the Mid-Ohio Valley has been contaminated with perfluorooctanoic acid (PFOA), which was released by a nearby DuPont chemical plant. Two highly contaminated water districts began granular activated carbon filtration in 2007. To determine the rate of decline in serum PFOA, and its corresponding half-life, during the first year after filtration. Up to six blood samples were collected from each of 200 participants from May 2007 until August 2008. The primary source of drinking water varied over time for some participants; our analyses were grouped according to water source at baseline in May-June 2007. For Lubeck Public Service District customers, the average decrease in serum PFOA concentrations between May-June 2007 and May-August 2008 was 32 ng/mL (26%) for those primarily consuming public water at home (n = 130), and 16 ng/mL (28%) for those primarily consuming bottled water at home (n = 17). For Little Hocking Water Association customers, the average decrease in serum PFOA concentrations between November-December 2007 and May-June 2008 was 39 ng/mL (11%) for consumers of public water (n = 39) and 28 ng/mL (20%) for consumers of bottled water (n = 11). The covariate-adjusted average rate of decrease in serum PFOA concentration after water filtration was 26% per year (95% confidence interval, 2528% per year). The observed data are consistent with first-order elimination and a median serum PFOA half-life of 2.3 years. Ongoing follow-up will lead to improved half-life estimation.


Sexual isolation and cuticular hydrocarbon differences between Drosophila santomea and Drosophila yakuba.
Drosophila santomea and Drosophila yakuba are two sister species inhabiting Saõ Tomé island. Previous studies showed that both species display strong reproductive isolation, although they can produce a few viable hybrids. Our study tried to understand the mechanism of this ethological isolation between two allopatric strains. A strong sexual isolation was confirmed, with a marked asymmetry. Comparisons of latency times to either courtship or copulation suggest that males do not discriminate females, whereas D. yakuba females, but not D. santomea females, accept their homospecifics more quickly. Cuticular hydrocarbon compositions of both species and sexes were also established with gas chromatography (GC) and GC/mass spectrometry analysis. All have (Z)-7-tricosene as their major compound. There are several quantitative differences between species for few minor compounds. The largest difference concerns n-heneicosane, which is more abundant in D. santomea than in D. yakuba flies (up to seven times more between males). A similar quantitative difference was also found in a pair of sympatric strains. Furthermore, D. yakuba males artificially perfumed with n-heneicosane were discriminated negatively by D. yakuba females, suggesting a role for this compound in the sexual isolation between these two species.


Natural history and management of congenital hypothyroidism with in situ thyroid gland.
Normally sited glands account for increasing congenital hypothyroidism (CH). Mechanisms often remain unknown. To report the incidence of CH with in situ thyroid gland (ISTG) and describe the natural history of the disease without known etiology. Clinical, biochemical and imaging data at diagnosis were retrospectively analyzed in 285 children positively screened for CH in Ile-de-France between 2005 and 2008. If treatment was discontinued, management of hormonal substitution and follow-up of biochemical thyroid function was performed. 93 full-term CH neonates displayed ISTG (40.6%), including 50 with unexplained mechanism. Follow-up data were available in 32 of them. Therapy was withdrawn from 20 children at a median age of 23.5 months (6-66), among whom 18 remained still untreated over a median duration of 15.3 months (4.4-29.6). In 11 children, levothyroxine (L-T4) dosage was increased over time to maintain biochemical euthyroidism. No statistical differences in initial TSH or FT4 levels, iodine status or birth weight were found between children with transient and permanent hypothyroidism. Withdrawal of L-T4 substitution was feasible in 56.2% of full-term children with CH with ISTG but unexplained mechanism, emphasizing the need for systematic therapy withdrawal. However, further studies are warranted to standardize withdrawal protocol.


Testing the methodology for a dosimetric end-to-end audit of IMRT/VMAT: results of IAEA multicentre and national studies.
Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented.Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations.Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within ±5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria.Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.


Making sense of music: Insights from neurophysiology and connectivity analyses in naturalistic listening conditions.
According to the latest frameworks, auditory perception and memory involve the constant prediction of future sound events by the brain, based on the continuous extraction of feature regularities from the environment. The neural hierarchical mechanisms for predictive processes in perception and memory for sounds are typically studied in relation to simple acoustic features in isolated sounds or sound patterns inserted in highly certain contexts. Such studies have identified reliable prediction formation and error signals, e.g., the N100 or the mismatch negativity (MMN) evoked responses. In real life, though, individuals often face situations in which uncertainty prevails and where making sense of sounds becomes a hard challenge. In music, not only deviations from predictions are masterly set up by composers to induce emotions but sometimes the sheer uncertainty of sound scenes is exploited for aesthetic purposes, especially in compositional styles such as Western atonal classical music. In very recent magnetoencephalography (MEG) and electroencephalography (EEG) studies, experimental and technical advances in stimulation paradigms and analysis approaches have permitted the identification of prediction-error responses from highly uncertain, atonal contexts and the extraction of prediction-related responses from real, continuous music. Moreover, functional connectivity analyses revealed the emergence of cortico-hippocampal interactions during the formation of auditory memories for more predictable vs. less predictable patterns. These findings contribute to understanding the general brain mechanisms that enable us to predict even highly uncertain sound environments and to possibly make sense of and appreciate even atonal music.


Precurved Cochlear Implants and Tip Foldover: A Cadaveric Imaging Study.
Objective This study aims to define a reliable protocol for radiographic identification of placement and tip foldover of newly designed precurved and straight electrodes. Study Design Prospective imaging study. Setting Academic institution. Methods Three models of cochlear implants (Cochlear, MED-EL, and Advanced Bionics) were inserted into fresh cadaveric specimens (n = 2) in 3 configurations (normal positioning in the scala tympani, intracochlear tip foldover, and placement into the vestibular system) for a total of 9 implant scenarios. Specimens were imaged with plain radiography in Stenvers projection, as well as by high-resolution computed tomography. Results Electrode placement and presence or absence of electrode tip foldover were easily identified in all 9 scenarios on plain radiography based on the described technique. Each was confirmed with high-resolution computed tomography. Plain film temporal bone images of new electrode designs with proper and improper placement are provided for reference. Conclusion A defined protocol for intraoperative plain film radiography allowed for reliable imaging of 3 newly designed cochlear implant electrodes and immediate identification of extracochlear placement and tip foldover. Findings may be used for intraoperative confirmation of electrode array placement.


Secondary diphosphine and diphosphido ligands: synthesis, characterisation and group 1 coordination compounds.
Two types of secondary diphosphines, 1,8-(ArPH)2C14H8 (1a: Ar = Tripp, 2,4,6-triisopropylphenyl; 1b: Ar = Mes, 2,4,6-trimethylphenyl) and 1,3-((t)BuPHCH2)2C6H4 (2), based on rigid 1,8-anthracene and flexible m-xylyl frameworks, respectively, have been synthesized using different strategies. Compounds 1a and 1b were formed by nucleophilic aromatic substitution of a potassium organophosphido salt onto 1,8-difluoroanthracene, while compound 2 was obtained by addition of the Grignard reagent [1,3-(ClMgCH2)2C6H4]x to a dichloroorganophosphine, followed by reduction to the diphosphine. These compounds were isolated as ca. 1 : 1 mixtures of rac and meso diastereomers as determined by multinuclear NMR spectroscopy. Borane and selenide derivatives of 2, 1,3-((t)BuPH(BH3)CH2)2C6H4 (3) and 1,3-((t)BuPH(Se)CH2)2C6H4 (4), were obtained. Preferential crystallization of one diastereomer of 3 and 4 was observed; X-ray crystallographic studies identified this as the rac isomer for diselenide 4. Metallation studies of compounds 1a and 2 yielded several alkali metal salts. The reaction of KH or K metal with 1a yielded the compounds 1,8-(TrippPK)2C14H8·xTHF (5) and 1,8-(TrippPK)2C14H10·xTHF (6), respectively; in complex 6 the central aromatic ring has been reduced to yield a bent dihydroanthracene backbone. A crown ether derivative of 6, [K(18-crown-6)(THF)2]2[1,8-(TrippP)2C14H10] (7), was characterised crystallographically. Double deprotonation of compound 2 with (n)BuLi/TMEDA (TMEDA = N,N,N',N'-tetramethylethylenediamine) afforded the yellow dilithium complex 1,3-((t)BuPLiCH2)2C6H4·TMEDA (8), which crystallized as a dimer featuring lithium-arene π interactions.


Dose-dependent pharmacokinetics of diflunisal in rats: dual effects of protein binding and metabolism.
The purpose of this study was to define the dual effects of saturable metabolism and saturable protein binding on the pharmacokinetics of diflunisal. Steady-state diflunisal concentration and its unbound fraction were examined in seven groups of rats to determine the relationships of infusion rate, concentration and total and unbound clearances. The total body plasma clearance decreased initially and then went up as the concentration of diflunisal increased, whereas the intrinsic clearance of unbound drug decreased with increasing concentration. The former is a consequence of saturable metabolism as well as saturable protein binding; the latter is a consequence of saturable metabolism. The fraction of unbound diflunisal increased with concentration. The biliary excretion data of ester and ether glucuronide suggested that both the ester and ether glucuronidation processes are capacity-limited, although the enzyme system for ether glucuronide has a lower Km and capacity than the system responsible for the ester glucuronidation.


Weighted data gravitation classification for standard and imbalanced data.
Gravitation is a fundamental interaction whose concept and effects applied to data classification become a novel data classification technique. The simple principle of data gravitation classification (DGC) is to classify data samples by comparing the gravitation between different classes. However, the calculation of gravitation is not a trivial problem due to the different relevance of data attributes for distance computation, the presence of noisy or irrelevant attributes, and the class imbalance problem. This paper presents a gravitation-based classification algorithm which improves previous gravitation models and overcomes some of their issues. The proposed algorithm, called DGC+, employs a matrix of weights to describe the importance of each attribute in the classification of each class, which is used to weight the distance between data samples. It improves the classification performance by considering both global and local data information, especially in decision boundaries. The proposal is evaluated and compared to other well-known instance-based classification techniques, on 35 standard and 44 imbalanced data sets. The results obtained from these experiments show the great performance of the proposed gravitation model, and they are validated using several nonparametric statistical tests.


What About the Men? A Critical Review of Men's Experiences of Intimate Partner Violence.
Intimate partner violence (IPV) is a health problem affecting people of all genders and other social locations. While IPV victimization of cis-gendered women has been widely researched, how men conceptualized or experience IPV victimization, and the variations in their experiences of IPV, has not been thoroughly examined. In this critical review of men's experiences of IPV, an extensive search of peer reviewed literature was conducted using multiple database (Cochrane database, MEDLINE, CINAHL, Embase, PsycgINFO, and Google Scholar) as well as the gray literature. We critically reviewed examining the conceptual foundations of IPV victimization among men. The influence or gender roles and societal expectation on men's experiences and perceptions of IPV victimization and their help-seeking behavior are explored. Current knowledge about types, tactics, and patterns of IPV against men and the health and social consequences of IPV are addresses. Additionally, the conceptual and empirical limitations of current research are discussed, including the tendency to compare only the prevalence rates of discrete incidents of abuse among women versus men; the use of IPV measures not designed to capture men's conceptualizations of IPV; and the lack of attention given to sex and gender identity of both the victim and perpetrator. Future research priorities that address these limitations and seek to strengthen and deepen knowledge about IPV among men are identified.


Effects of second-generation tyrosine kinase inhibitors towards osteogenic differentiation of human mesenchymal cells of healthy donors.
The BCR-ABL inhibitor imatinib is a standard first-line therapy for patients with chronic myeloid leukemia. However, it has been demonstrated that this long-term treatment is associated with altered bone metabolism. The mechanisms of this effect are not fully understood, but an inhibition of the platelet-derived growth factor receptor (PDGF-R) β axis has been suspected on the basis of some in vitro findings. We evaluated the osteoblastic differentiation of mesenchymal stem cells derived from bone marrow (hBM-MSCs) after in vitro treatment with dasatinib, nilotinib or bosutinib. Human bone marrow mesenchymal stem cells were induced to differentiate in osteoblastic cells by treatment with osteogenic medium with or without dasatinib, nilotinib or bosutinib. We found that the addition of dasatinib, and to a greater extend nilotinib, induced expression of osteogenic mRNA markers as compared with cultures with standard medium or osteogenic medium only. However, treatment with bosutinib did not induce an increase of osteogenic markers. In conclusion, we show that besides imatinib, other tyrosine kinase inhibitors (TKIs) such as dasatinib and nilotinib, but not bosutinib, increase osteogenic markers in hBM-MSCs. Because bosutinib differs from the other TKIs because of its low affinity to other kinases such as PDGF-R, these experiments suggest that inhibition of PDGF-R may be involved in the induction of osteoblastogenesis by TKIs.


Reproducible metabolic topographies associated with multiple system atrophy: Network and regional analyses in Chinese and American patient cohorts.
Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson's disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts. We included 18F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnosis among moderate- and early-stage MSA, PSP or PD patients and clinical correlations with disease severity. Regional metabolic differences were detected using statistical parameter mapping analysis. MSA-related network and regional topographies of metabolic abnormality were cross-validated between the Chinese and American cohorts. We generated a highly reliable MSAPRP characterized by decreased loading in inferior frontal cortex, striatum and cerebellum, and increased loading in sensorimotor, parietal and occipital cortices. MSAPRP scores discriminated between normal, MSA, PSP and PD subjects and correlated with standardized ratings of clinical stages and motor symptoms in MSA. High similarities in MSAPRPs, network scores and corresponding maps of metabolic abnormality were observed between two different cohorts. We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.


A comparative validation of the Foulds and Bedford hierarchy of psychiatric symptomatology.
This study investigated the validity of the Fould & Bedford hierarchical model of psychiatric illness, as compared to hierarchical models based upon prevalence and severity of disorder. The DSSI was administered to 52 American psychiatric in-patients with severe disturbances. The reports of symptoms in this sample conformed to the Foulds hierarchy in 90% of cases, while 94% of cases conformed to a model based upon prevalence. When a cross-method validation was investigated, the Foulds & Bedford classification demonstrated good discriminative capacity, while models based upon prevalence and severity failed to achieve significance. These results suggest that the Foulds & Bedford model is a useful taxonomy of symptomatology in psychiatric illness.


Pharmacokinetics of phenoperidine in patients undergoing cardiopulmonary bypass.
Phenoperidine concentrations were studied, using radioimmunoassay, in five patients submitted to coronary artery bypass graft surgery. Administration of phenoperidine consisted of a 5-mg bolus dose followed by constant infusion of 5 mg h-1. Before cardiopulmonary bypass, phenoperidine concentrations were stable in an individual patient, but there was a large scatter between patients. The concentrations decreased immediately following the start of the bypass, but this decrease was short. During cardiopulmonary bypass, the phenoperidine concentrations increased progressively and were greater at the end of the bypass than before it. The increase in concentration continued following the discontinuation of bypass. The ratios of change of the observed results were in accord with a theoretical evaluation, although the observed concentrations were all greater than those calculated, except at one point. This difference in phenoperidine concentration is probably related to an alteration of liver plasma flow. Haemodilution as a result of the priming of the cardiopulmonary bypass circuit played only a transient role.


[Pseudo-anemia caused by sports].
Regular physical training leads to an increase of plasma volume by 10-20 percent. Therefore, hemoglobin concentration slightly below normal values in the presence of low-normal serum ferritin levels in athletes are usually due to a dilutional "pseudoanemia". Several cross sectional studies indicate that true iron deficiency anemia is not more frequent in athletes than in the general population. Since regular physical activity, especially extensive, running increases iron loss, mild iron deficiency (abnormal serum ferritin and normal hemoglobin concentration) and sometimes true iron deficiency anemia can occur especially when nutritional iron intake is insufficient and iron demand is increased because of growth (children, adolescents) or additional iron loss (menstruation). Several controlled studies indicate that iron supplementation (recommended dose 2 x 100 mg elementary iron/day) improves performance only when hemoglobin concentration increases, i.e. when iron deficiency anemia is present. On the contrary, iron supplementation has no measurable effects on performance when hemoglobin concentration cannot be increased, i.e. in mild iron deficiency.


Formation of water-soluble complex between the 1-34 fragment of parathyroid hormone and dimyristoylphosphatidylcholine.
Two biologically active, 34 amino acid fragments of parathyroid hormone interact with dimyristoylphosphatidylcholine to form lipoprotein particles. In the lipid-bound form these parathyroid hormone peptides exhibit an increased amount of folded secondary structure and the tryptophan residue of [Nle8, Nle18, Tyr34] b PTH (1-34) amide appears to become buried in a more hydrophobic environment. The lipoprotein particle which is formed has dimensions of approximately 65 X 7 nm but aggregates to larger structures with increasing temperature. Above the phase transition of the phospholipid the peptides no longer affect the morphology of the lipid and the spectral properties of the peptide are not perturbed by the lipid. This is similar to the behavior of glucagon with dimyristoylphatidylcholine. The results indicate that several nonhomologous peptide hormones have common features which allow them to fold into an amphipathic helix and solubilize phospholipid.


Treosulfan Exposure Predicts Thalassemia-Free Survival in Patients with Beta Thalassemia Major Undergoing Allogeneic Hematopoietic Cell Transplantation.
A toxicity-reduced conditioning regimen with treosulfan, fludarabine, and thiotepa in patients with high-risk β-thalassemia major has significantly improved hematopoietic stem cell transplantation (HCT) outcomes. However, complications resulting from regimen-related toxicities (RRTs), mixed chimerism, and graft rejection remain a challenge. We evaluated the dose-exposure-response relationship of treosulfan and its active metabolite S, S-EBDM, in a uniform cohort of patients with β-thalassemia major to identify whether therapeutic drug monitoring (TDM) and dose adjustment of treosulfan is feasible. Plasma treosulfan/S, S-EBDM levels were measured in 77 patients using a validated liquid chromatography with tandem mass spectrometry method, and the pharmacokinetic parameters were estimated using nlmixr2. The influence of treosulfan and S, S-EBDM exposure, and GSTA1/NQO1 polymorphisms on graft rejection, RRTs, chimerism status, and 1-year overall survival (OS), and thalassemia-free survival (TFS) were assessed. We observed that treosulfan exposure was lower in patients with graft rejection than those without (1,655 vs. 2,037 mg•h/L, P = 0.07). Pharmacodynamic modeling analysis to identify therapeutic cutoff revealed that treosulfan exposure ≥1,660 mg•hour/L was significantly associated with better 1-year TFS (97% vs. 81%, P = 0.02) and a trend to better 1-year OS (90% vs. 69%, P = 0.07). Further, multivariate analysis adjusting for known pre-HCT risk factors also revealed treosulfan exposure <1,660 mg•h/L (hazard ratio (HR) = 3.23; 95% confidence interval (CI) = 1.12-9.34; P = 0.03) and GSTA1*B variant genotype (HR = 3.75; 95% CI = 1.04-13.47; P = 0.04) to be independent predictors for inferior 1-year TFS. We conclude that lower treosulfan exposure increases the risk of graft rejection and early transplant-related mortality affecting TFS. As no RRTs were observed with increasing treosulfan exposure, TDM-based dose adjustment could be feasible and beneficial.


Long-term evaluation of osseointegrated implants placed in sites augmented with sinus floor elevation associated with vertical ridge augmentation: a retrospective study of 38 consecutive implants with 1- to 7-year follow-up.
This clinical study retrospectively evaluated, after 1 to 7 years of prosthetic loading, 38 implants consecutively placed in 16 surgical sites, where severe atrophy of the posterior maxilla was treated by combining sinus elevation with the vertical ridge regenerative procedure. Two different surgical techniques were adopted. In seven patients (16 implants), implants were placed at the same stage as the regenerative procedures. In the other seven patients (22 implants), implant placement was performed at second-stage surgery, after 6 to 13 months of submerged membrane healing. Each implant was classified as a success, survival, or failure. The distance between the top of the implant shoulder and the first visible bone-implant contact was assessed radiographically for every implant at the mesial and distal sides. Two membranes became exposed during the healing process (12.5%). In the remaining 14 sites (87.5%), the membrane remained covered for a 6- to 13-month healing period. The survival rate of the implants was 92.1%, whereas the success rate was 76.3%. Three implants (7.9%) failed. A comparison of the implant shoulder-bone-implant contact distances between abutment connection and the last examination showed a mean crestal loss of 1.65 mm at the mesial side and 1.68 mm at the distal side. The bone regenerated vertically by means of sinus floor elevation and vertical ridge augmentation showed the same biologic behavior as native, nonregenerated bone; however, in a few cases, its remodeling pattern seemed to determine slightly higher bone crest resorption.


Effect of phantom voxelization in CT simulations.
In computer simulations of x-ray CT systems one can either use continuous geometrical descriptions for phantoms or a voxelized representation. The voxelized approach allows arbitrary phantoms to be defined without being confined to geometrical shapes. The disadvantage of the voxelized approach is that inherent errors are introduced due to the phantom voxelization. To study effects of phantom discretization, analytical CT simulations were run for a fan-beam geometry with phantom voxel sizes ranging from 0.0625 to 2 times the reconstructed pixel size and noise levels corresponding to 10(3) - 10(7) photons per detector pixel prior to attenuation. The number of rays traced per detector element was varied from 1 to 16. Differences in the filtered backprojection images caused by changing the phantom matrix sizes and number of rays traced were assessed by calculating the difference between reconstructions based on the finest matrix and coarser matrix simulations. In noise free simulations, all phantom matrix sizes produced a measurable difference in comparison with the finest phantom matrix used. When even a small amount of noise was added to the projection data, the differences due to the phantom discretization were masked by the noise, and in all cases there was almost no improvement by using a phantom matrix that was more than twice as fine as the reconstruction matrix. No substantial improvement was achieved by tracing more than 4 rays per detector pixel.


Visual experience and plasticity of the visual cortex: a role for epigenetic mechanisms.
Plasticity of cortical circuits is maximal during critical periods of postnatal development. Ocular dominance plasticity is a classical model to understand the role of experience in development of the visual cortex. Recent studies are beginning to unravel the synaptic mechanisms underlying this form of plasticity and to elucidate the different plasticity of juvenile and adult animals at mechanistic and molecular level. These investigations indicate that this form of plasticity is regulated by factors located at extracellular and intracellular level. The molecular composition of the extracellular environment in which synaptic plasticity occurs changes during development becoming less permissive for plasticity. In addition, visual experience activates epigenetic mechanisms of regulation of gene transcription that becomes downregulated in adult animals.


Principles of image processing in digital chest radiography.
Image processing has a major impact on image quality and diagnostic performance of digital chest radiographs. Goals of processing are to reduce the dynamic range of the image data to capture the full range of attenuation differences between lungs and mediastinum, to improve the modulation transfer function to optimize spatial resolution, to enhance structural contrast, and to suppress image noise. Image processing comprises look-up table operations and spatial filtering. Look-up table operations allow for automated signal normalization and arbitrary choice of image gradation. The most simple and still widely applied spatial filtering algorithms are based on unsharp masking. Various modifications were introduced for dynamic range reduction and MTF restoration. More elaborate and more effective are multi-scale frequency processing algorithms. They are based on the subdivision of an image in multiple frequency bands according to its structural composition. This allows for a wide range of image manipulations including a size-independent enhancement of low-contrast structures. Principles of the various algorithms will be explained and their impact on image appearance will be illustrated by clinical examples. Optimum and sub-optimum parameter settings are discussed and pitfalls will be explained.


Heterologous sequences greatly affect foreign gene expression in tobacco mosaic virus-based vectors.
A series of tobacco mosaic virus (TMV)-based hybrid vectors for transient gene expression were constructed with similar designs but differing in the source of heterologous tobamovirus sequence: Odontoglossum ringspot virus, tobacco mild green mosaic virus variants U2 and U5, tomato mosaic virus, and sunn-hemp mosaic virus. These vectors contained a heterologous coat protein subgenomic mRNA promoter and coat protein open reading frame (ORF) and either TMV or heterologous 3' nontranslated region. The foreign ORF, from the jellyfish green fluorescent protein (GFP) gene, was transcribed from the native TMV coat protein subgenomic mRNA promoter, which extended into the coat protein ORF. The presence of an in-frame stop codon within the GFP mRNA leader and the choice of sequence of GFP ORFs substantially affected translational efficiency. However, the major regulatory component of gene expression in these vectors appeared to be transcriptional rather than translational. There was an inverse relationship between expression of GFP and the heterologous coat protein genes that was reflected in accumulation of the respective mRNAs and proteins. The most effective vector in this series (30B) contained sequences encoding the coat protein subgenomic mRNA promoter, coat protein ORF, and 3' nontranslated region from tobacco mild green mosaic virus U5. Expressed from 30B, GFP accumulated up to 10% of total soluble protein in leaves.


Drosophila mitochondrial transcription factor B2 regulates mitochondrial DNA copy number and transcription in schneider cells.
We report the cloning and molecular analysis of Drosophila mitochondrial transcription factor B2 (d-mt-TFB2), a protein that plays a role in mitochondrial transcription and mitochondrial DNA (mtDNA) replication in Drosophila. An RNA interference (RNAi) construct was designed that reduces expression of d-mtTFB2 to 5% of its normal level in Schneider cells. RNAi knock-down of d-mtTFB2 reduces the abundance of specific mitochondrial RNA transcripts 2- to 8-fold and decreases the copy number of mtDNA approximately 3-fold. In a corollary manner, we find that overexpression of d-mtTFB2 increases both the abundance of mitochondrial RNA transcripts and the copy number of mtDNA. In a comparative experiment, we find that overexpression of Drosophila mitochondrial transcription factor A (d-TFAM) increases mtDNA copy number with no significant effect on mitochondrial transcripts. This argues for a direct role for mtTFB2 in mitochondrial transcription and suggests that, if TFAM serves a role in transcription, its endogenous level limits mtDNA copy number but not transcription. Furthermore, we suggest that mtTFB2 increases mtDNA copy number by increasing the frequency of initiation of DNA replication, whereas TFAM serves to stabilize and package mtDNA in mitochondrial nucleoids. Our work represents the first study to document the function of mtTFB2 in vivo, establishing a dual role in regulation of both transcription and replication, and provides a benchmark for comparative biochemical studies in various animal systems.


Effects of anti-tumor necrosis factor α agents on bone.
Tumor necrosis factor (TNF) inhibitors are effective for achieving disease control in several inflammatory diseases. Although anti-TNF agents can inhibit bone loss in vitro, their role in the prevention of clinically relevant outcomes such as osteoporosis and fractures has not been clearly established. There are many studies of the effects of TNF inhibitors on markers of bone turnover; however, few have measured bone mineral density (BMD) or fractures. Most of these studies have small sample sizes and a minority had a placebo control group. Overall these studies suggest that the antiresorptive effects of anti-TNF therapy are related to control of disease activity. The antiresorptive effects of TNF inhibitors are likely related to their anti-inflammatory properties. Studies to date have not demonstrated any advantages of TNF inhibitors over traditional nonbiologic therapies in the prevention of bone loss and fractures.


Unripe Pear Extract Suppresses UVB-Induced Skin Photoaging in Hairless Mice and Keratinocytes.
Our study aimed to investigate whether unripe pear extract (UP) could provide protection against UVB-induced damage to both mouse skin and keratinocytes. We observed that UVB exposure, a common contributor to skin photoaging, led to wrinkle formation, skin dryness, and inflammation in mice. Nevertheless, these effects were mitigated in the groups of UVB-irradiated mice treated with UP. Moreover, UP treatment at 400 μg/mL increased the antioxidant enzyme activities (sodium dodecyl sulfate, 2.22-fold higher; catalase, 2.91-fold higher; GPx, 1.96-fold higher) along with sphingomyelin (1.58-fold higher) and hyaluronic acid (1.31-fold higher) levels in UVB-irradiated keratinocytes. In the keratinocytes irradiated with UVB, UP 400 μg/mL resulted in reduced cytokine production (TNF-α, 33.2%; IL-1β, 45.3%; IL-6, 33.4%) and the expression of inflammatory pathway-related proteins. The findings indicate that UP has a direct protective effect on UVB-irradiated keratinocytes and is also able to shield against photoaging induced by UVB. Hence, it is suggested that UP could contribute to improved skin health by averting skin photoaging.


The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity.
Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29-100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.


A novel model of drug hapten-induced hepatitis with increased mast cells in the BALB/c mouse.
Clinical evidence suggests that idiosyncratic hepatitis following administration of halogenated volatile anesthetics is mediated by autoimmune responses. No murine model to study mechanisms of anesthetic-induced or any other form of drug-induced idiosyncratic hepatitis exists. Anesthetics are believed to trigger hepatitis by covalently linking a trifluoroacetyl (TFA) chloride hapten to hepatic proteins, forming haptenated self-proteins. To test this hypothesis, we developed a hapten-induced model of hepatitis by immunization with syngeneic S100 liver proteins covalently coupled to TFA (TFA-S100). We found that TFA-S100 induced hepatitis was more severe than disease induced by S100 plus adjuvants or by the adjuvant alone and was characterized by neutrophil, mast cell, and eosinophil infiltration. TFA-specific IgG1 antibodies directly correlated with hepatitis, whereas S100 autoantibodies did not. TNF-alpha, IL-1beta, and IL-6 released from splenocytes collected 2 weeks after TFA-S100 inoculation were increased resembling the elevated serum cytokines reported in patients with autoimmune hepatitis (AIH). Three weeks after inoculation, the peak of hepatitis, we noted decreased numbers of Kupffer cells and lower levels of IL-6 and IL-10 in the liver, cytokines produced by Kupffer cells. This is the first report, to our knowledge, of a hapten-induced model of hepatitis with immune and autoimmune features.


Do the five A's work when physicians counsel about weight loss?
More than two thirds of Americans are overweight or obese. Physician counseling may help patients lose weight; however, physicians perceive these discussions as somewhat futile and time-consuming. An effective and efficient tool for smoking cessation is the Five A's (Ask, Advise, Assess, Assist, and Arrange). We studied the effectiveness of the Five A's in weight-loss counseling. We audiorecorded primary care encounters between 40 physicians and 461 of their overweight or obese patients. All were told the study was about preventive health, not weight specifically. Encounters were coded for physician use of the Five A's. Patients' motivation and confidence were assessed before and immediately after the encounter. Three months later, we assessed patient change in dietary fat intake, exercise, and weight. Generalized linear models were fit adjusting for patient clustering within physician. Physicians used at least one of the Five A's often (83%). Physicians routinely Ask and Advise patients to lose weight; however, they rarely Assess, Assist, or Arrange. Assist and Arrange were related to diet improvement, whereas Advise was associated with increases in motivation and confidence to change dietary fat intake and confidence to lose weight. Similar to smoking cessation counseling, physicians routinely Asked and Advised patients to lose weight; however, they rarely Assessed, Assisted, or Arranged. Given the potential impact of using all of these counseling tools on changing patient behavior, physicians should be encouraged to increase their use of the Five A's when counseling patients to lose weight.


Transient expression of MIDC-8 in the normal mouse brain.
In this study, we have immunohistochemically characterized the expression of mononuclear phagocyte markers CD14, CD36, CD68, CD204 and MARCO by parenchymal microglia in the developing and adult mouse brain. We further investigated whether these cells express two well-characterized phenotypic markers of dendritic cells: CD205 (DEC-205/NLDC-145) and MIDC-8 antigen. Our results confirm the lack of expression of dendritic cell markers by microglia. We noted that these cells do not appear to express markers associated with monocytes and macrophages during the course of development, but do express CD68 and CD204 antigens in the adult. Unexpectedly, we also noted the transient expression of MIDC-8 antigen on cells within the medial ganglionic eminence and by neuroepithelial cells lining the lateral ventricles and in the medial lemniscus between E15 and E19. We discuss this finding in the context of neural and haematopoietic differentiation.


Speech technology-based assessment of phoneme intelligibility in dysarthria.
Currently, clinicians mainly rely on perceptual judgements to assess intelligibility of dysarthric speech. Although often highly reliable, this procedure is subjective with a lot of intrinsic variables. Therefore, certain benefits can be expected from a speech technology-based intelligibility assessment. Previous attempts to develop an automated intelligibility assessment mainly relied on automatic speech recognition (ASR) systems that were trained to recognize the speech of persons without known impairments. In this paper automatic speech alignment (ASA) systems are used instead. In addition, previous attempts only made use of phonemic features (PMF). However, since articulation is an important contributing factor to intelligibility of dysarthric speech and since phonological features (PLF) are shared by multiple phonemes, phonological features may be more appropriate to characterize and identify dysarthric phonemes. To investigate the reliability of objective phoneme intelligibility scores obtained by three types of intelligibility models: models using only phonemic features (yielded by an automated speech aligner) (PMF models), models using only phonological features (PLF models), and models using a combination of phonemic and phonological features (PMF + PLF models). Correlations were calculated between the objective phoneme intelligibility scores of 60 dysarthric speakers and the corresponding perceptual phoneme intelligibility scores obtained by a standardized perceptual phoneme intelligibility assessment. The correlations between the objective and perceptual intelligibility scores range from 0.793 for the PMF models, over 0.828 for PLF models to 0.943 for PMF + PLF models. The features selected to obtain such high correlations can be divided into six main subgroups: (1) vowel-related phonemic and phonological features, (2) lateral-related features, (3) silence-related features, (4) fricative-related features, (5) velar-related features and (6) plosive-related features. The phoneme intelligibility scores of dysarthric speakers obtained by the three investigated intelligibility model types are reliable. The highest correlation between the perceptual and objective intelligibility scores was found for models combining phonemic and phonological features. The intelligibility scoring system is now ready to be implemented in a clinical tool.


The frequency-dependent directivity of a planar fabry-perot polymer film ultrasound sensor.
A model of the frequency-dependent directivity of a planar, optically-addressed, Fabry-Perot (FP), polymer film ultrasound sensor is described and validated against experimental directivity measurements made over a frequency range of 1 to 15 MHz and angles from normal incidence to 80 degrees. The model may be used, for example, as a predictive tool to improve sensor design, or to provide a noise-free response function that could be deconvolved from sound-field measurements in order to improve accuracy in high-frequency metrology and imaging applications. The specific question of whether effective element sizes as small as the optical-diffraction limit can be achieved was investigated. For a polymer film sensor with a FP cavity of thickness d, the minimum effective element radius was found to be about 0.9 d, and that an illumination spot radius of less than d/4 is required to achieve it.


Imaging Features of Primary Tumors of the Hand.
Musculoskeletal tumors of the hand are a rare entity and are divided into skeletal and soft tissue tumors. Either category comprises benign and malignant or even intermediate tumors. Basic radiology allows an optimal resolution of bone and related soft tissue areas, ultrasound and more sophisticated radiologic tools such as scintigraphy, CT and MRI allow a more accurate evaluation of tumor extent. Enchondroma is the most common benign tumor affecting bone, whereas chondrosarcoma is the most commonly represented malignant neoplasm localized to hand bones. In the soft tissues, ganglions are the most common benign tumors and epithelioid sarcoma is the most frequently represented malignant tumor targeting hand soft tissues. The knowledge regarding diagnostic and therapeutic management of these tumors is often deriving from small case series, retrospective studies or even case reports. Evidences from prospective studies or controlled trials are limited and for this lack of clear and supported evidences, data from the medical literature on the topic are controversial, in terms of demographics, clinical presentation, diagnosis, prognosis and therapy. The correct recognition of the specific subtype and extension of the tumor through first line and second line radiology is essential for the surgeon, in order to effectively direct the therapeutic decisions.


Identification and characterization of MAE1, the Saccharomyces cerevisiae structural gene encoding mitochondrial malic enzyme.
Pyruvate, a precursor for several amino acids, can be synthesized from phosphoenolpyruvate by pyruvate kinase. Nevertheless, pyk1 pyk2 mutants of Saccharomyces cerevisiae devoid of pyruvate kinase activity grew normally on ethanol in defined media, indicating the presence of an alternative route for pyruvate synthesis. A candidate for this role is malic enzyme, which catalyzes the oxidative decarboxylation of malate to pyruvate. Disruption of open reading frame YKL029c, which is homologous to malic enzyme genes from other organisms, abolished malic enzyme activity in extracts of glucose-grown cells. Conversely, overexpression of YKL029c/MAE1 from the MET25 promoter resulted in an up to 33-fold increase of malic enzyme activity. Growth studies with mutants demonstrated that presence of either Pyk1p or Mae1p is required for growth on ethanol. Mutants lacking both enzymes could be rescued by addition of alanine or pyruvate to ethanol cultures. Disruption of MAE1 alone did not result in a clear phenotype. Regulation of MAE1 was studied by determining enzyme activities and MAE1 mRNA levels in wild-type cultures and by measuring beta-galactosidase activities in a strain carrying a MAE1::lacZ fusion. Both in shake flask cultures and in carbon-limited chemostat cultures, MAE1 was constitutively expressed. A three- to fourfold induction was observed during anaerobic growth on glucose. Subcellular fractionation experiments indicated that malic enzyme in S. cerevisiae is a mitochondrial enzyme. Its regulation and localization suggest a role in the provision of intramitochondrial NADPH or pyruvate under anaerobic growth conditions. However, since null mutants could still grow anaerobically, this function is apparently not essential.


Transgenic Arabidopsis leaf tissue expressing a modified oryzacystatin shows resistance to the field slug Deroceras reticulatum (Müller).
Transgenic Arabidopsis thaliana has been developed which expresses the oryzacystatin mutant OC-I delta 86, which is an inhibitor of the major proteinase present in the digestive gland of the slug, Deroceras reticulatum. When fed on leaf tissue from plants expressing this inhibitor the growth of juvenile slugs was significantly reduced by 31% compared with those feeding on control leaf tissue. Furthermore, while surviving slugs did not individually consume less when feeding on leaf tissue expressing OC-I delta 86, the total amount of leaf tissue eaten was 50% less, due to reduced survival of slugs. The synthetic cysteine proteinase inhibitors E-64 and leupeptin also significantly reduced slug weight gain (by at least 40%) and digestive gland cysteine proteinase activity when administered in an artificial diet, indicating that their antimetabolic effects are due to direct inhibition of gut proteolytic activity. These results suggest that transgenic crop plants expressing phytocystatins could be used to suppress the growth rates of slug populations in the field.


The use of person-first language in scientific literature focused on drug-seeking behavior: a cross-sectional analysis.
Person first language (PFL) - a way of referring to individuals with medical conditions or disability that emphasizes the person over their condition or disability - is important in reducing the stigma surrounding individuals who exhibit drug-seeking behavior. Drug-seeking behavior is generally associated with a negative connotation by healthcare professionals, which may create poor provider perceptions of these individuals and potentially impact patient care. Therefore, to reduce stigmatization surrounding drug-seeking behavior and to improve patient care in these individuals, the use of PFL should be promoted. The primary objective of this study is to investigate how frequently research articles focused on drug-seeking behavior adhere to PFL. We performed a cross-sectional analysis systematically searching PubMed for articles published between May 1, 2011, and April 30, 2020, focused on drug-seeking behavior. To be included, the article must have met the following criteria: (1) published in a peer-reviewed journal; (2) relevant to drug-seeking behavior; and (3) must include human subjects and be retrievable in English. All articles were screened and data were extracted independently in a masked, duplicate fashion. Each article was reviewed for 19 predefined non-PFL terms with certain terms adopted from the American Medical Association Manual of Style. Our search returned 699 articles related to drug-seeking behavior, of which 390 articles met inclusion criteria and were analyzed for non-PFL. Our analysis found only 13.6% (53/390) of articles adhered to PFL while 86.4% (337/390) of articles contained at least some form of non-PFL. There was no association between PFL adherence and extracted study characteristics. PFL adherence is uncommon among research literature focused on drug-seeking behavior. The power of language can be profound, and should be understood by researchers, health care providers, and educators alike, specifically when dealing with known and exhibited characteristics of substance use disorders. This is relevant because of the high prevalence of substance use disorders, limited amount of prior research, and the impact stigma has on patients and healthcare providers.


Exploring the experiences of young people nursed on adult wards.
This paper reports on a study of experiences of young people aged 14 to 18 years who were nursed on acute adult hospital wards in NHS hospitals in England. In spite of British government guidelines, young people from 14 years of age continue to be admitted to adult wards in the UK. Although much has been written about the transition of the young person to adult services, there is little research about the experiences of young people who are nursed on adult wards. Hermeneutic phenomenology was used to explore the lived experiences of eight young people who had been nursed on adult wards between 2004 and 2010. Data were collected in 2010. In-depth interviews were recorded, transcribed and analysed using Colaizzi's framework ( Colaizzi, 1978 ). Themes explored included expectations of what the experience may be like, young people's first impressions of the ward environment, the feelings of the young person while in hospital, the attitudes of people towards them including, both staff and other patients, and future admissions and how they would cope with readmissions. Better provision needs to be made for young people including appropriately trained staff, adolescent-friendly environments and areas in adult wards that are dedicated to adolescents.


Envelope instability in DNA adenine methylase mutants of Salmonella enterica.
Mutants of Salmonella enterica serovar Typhimurium lacking DNA adenine (Dam) methylase show reduced secretion of invasion effectors encoded in the Salmonella-pathogenicity island 1 (SPI-1). Concomitant with this alteration, a high number and quantity of extracellular proteins are detected in cultures of Dam(-) mutants. This study shows by subcellular fractionation analysis that the presence of numerous extracellular proteins in cultures of Dam(-) mutants is linked to an exacerbated release of membrane particulate material. The membrane 'leaky' phenotype and the impaired functionality of type III secretion systems were, however, unrelated since exacerbated release of proteins to the medium was evident in Dam(-) strains carrying mutations in either SPI-1 (invA, invJ) or flagellar (flhD) genes. This result supports the view that Dam methylation controls a plethora of cellular processes. Electron microscopy analysis demonstrated that the accumulation of membrane particulate material occurs preferentially as vesicles in stationary cultures of Dam(-) strains. In addition, a reduction in the relative amount of peptidoglycan-associated lipoprotein (PAL), TolB, OmpA and murein lipoprotein (Lpp) bound to peptidoglycan was observed in actively growing Dam(-) mutants. The existence of an envelope defect was further confirmed by the increased sensitivity to deoxycholate exhibited by Dam(-) mutants, mostly during exponential growth. Unexpectedly, lack of Dam methylation neither increased envelope instability nor impaired the association of PAL-Tol-Lpp proteins to the peptidoglycan in Escherichia coli. Accordingly, E. coli Dam(-) mutants did not show sensitivity to deoxycholate. Altogether, these results indicate that, besides its role in modulating the secretion of effectors by the SPI-1-encoded type III apparatus, Dam methylation controls cell envelope integrity in S. enterica.


Micro-morphologic changes around biophysically-stimulated titanium implants in ovariectomized rats.
Osteoporosis may present a risk factor in achievement of osseointegration because of its impact on bone remodeling properties of skeletal phsiology. The purpose of this study was to evaluate micro-morphological changes in bone around titanium implants exposed to mechanical and electrical-energy in osteoporotic rats. Fifteen 12-week old sprague-dowley rats were ovariectomized to develop osteoporosis. After 8 weeks of healing period, two titanium implants were bilaterally placed in the proximal metaphyses of tibia. The animals were randomly divided into a control group and biophysically-stimulated two test groups with five animals in each group. In the first test group, a pulsed electromagnetic field (PEMF) stimulation was administrated at a 0.2 mT 4 h/day, whereas the second group received low-magnitude high-frequency mechanical vibration (MECHVIB) at 50 Hz 14 min/day. Following completion of two week treatment period, all animals were sacrificed. Bone sites including implants were sectioned, removed en bloc and analyzed using a microCT unit. Relative bone volume and bone micro-structural parameters were evaluated for 144 mum wide peri-implant volume of interest (VOI). Mean relative bone volume in the peri-implant VOI around implants PEMF and MECHVIB was significantly higher than of those in control (P < .05). Differences in trabecular-thickness and -separation around implants in all groups were similar (P > .05) while the difference in trabecular-number among test and control groups was significant in all VOIs (P < .05). Biophysical stimulation remarkably enhances bone volume around titanium implants placed in osteoporotic rats. Low-magnitude high-frequency MECHVIB is more effective than PEMF on bone healing in terms of relative bone volume.


Tomographic abnormalities simulating pituitary microadenomas.
False-positive and false-negative interpretations of sellar tomography were found in about one-fifth of cases in a recent autopsy study correlating the presence of pituitary microadenomas with abnormal sellar tomograms. An analysis of minor variations in the bony configuration of the sella disclosed variations due to posterior lobe asymmetry, intercavernous venous channels, bony asymmetry, and an empty sella in 27 of the 120 sellas examined. In some instances, the asymmetry resulted from a combination of these causes. A further study of 50 pituitary glands in situ showed posterior lobe asymmetry to be a common anomaly (76%) that can produce an obvious disparity between the two halves of the sella. Thus, the minor radiologic criteria of local thinning of the anterior wall or floor, slant of the floor, or asymmetry of the two halves of the sella must be interpreted with caution as being indicative of the presence of pituitary microadenoma. In the absence of clinical or biochemical dysfunction, the changes more likely result from explainable anatomic causes.


What Have We Learned from Studies of IFN-λ Variants and Hepatitis C Virus Infection?
Chronic infection with the hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In 2009, genome-wide association studies (GWAS) strongly linked genetic variants in the interferon lambda (IFN-λ) chromosomal region to HCV clearance. In 2013, discovery of the IFNL4 gene provided a functional explanation for those GWAS findings. The IFNL4-ΔG/TT (rs368234815) variant controls generation of the IFN-λ4 protein. Paradoxically, the IFNL4-TT allele, which abrogates IFN-λ4, associates with higher rates of spontaneous HCV clearance and better response to treatments for HCV infection. The finding that a "knock-out" allele for IFN-λ4 enhances HCV clearance challenges the paradigm of IFNs as antiviral cytokines. Genetic variants in the IFN-λ region have also been associated with hepatic inflammation and fibrosis from various etiologies, however, alleles that are linked with improved HCV clearance associates with worse inflammation and fibrosis. These studies demonstrate that GWAS of infectious diseases may yield important and unexpected biological insights.


Impact of Agro-industrial Byproducts on Bioconversion, Chemical Composition, in vitro Digestibility, and Microbiota of the Black Soldier Fly (Diptera: Stratiomyidae) Larvae.
The interest in using byproducts from agro-food industries as a rearing substrate for insects is increasing rapidly. We investigated the influence of byproducts of vegetal origin (okara-a byproduct of soy milk production, maize distillers with solubles, brewer's grains), used as rearing diet for black soldier fly larvae (BSFL), on the following parameters: biomass production, substrate reduction (SR), nutritional profile and in vitro digestibility, and larval gut microbiota. Hen diet was used as a control substrate. The highest larval biomass was collected on maize distillers, whereas the highest SR was observed on okara. The rearing substrate affected ash, ether extract, and chitin larval content. The BSFL reared on okara were characterized by a lower lauric acid content (17.6% of total fatty acids). Diets also influenced in vitro crude protein digestibility (%) for monogastrics, with the highest values for BSFL reared on maize distillers (87.8), intermediate for brewer's grains and okara BSFL, and the lowest for hen BSFL (82.7). The nutritive value for ruminants showed a lower Net Energy for lactation for BSFL reared on hen diet than okara and dried maize distillers BSFL. The different byproducts showed an influence on the larval gut microbiota, with a major bacterial complexity observed on larvae fed with the hen diet. The neutral detergent fiber concentration of dietary substrate was negatively correlated with Firmicutes and Actinobacteria relative abundance. Insects valorized byproducts converting them into high-value larval biomass to be used for feed production. The results evidenced the effects of the tested byproducts on the measured parameters, underling the chemical composition importance on the final insect meal quality.


Impact of individual and environmental socioeconomic status on peritoneal dialysis outcomes: a retrospective multicenter cohort study.
We aimed to explore the impacts of individual and environmental socioeconomic status (SES) on the outcome of peritoneal dialysis (PD) in regions with significant SES disparity, through a retrospective multicenter cohort in China. Overall, 2,171 incident patients from seven PD centers were included. Individual SES was evaluated from yearly household income per person and education level. Environmental SES was represented by regional gross domestic product (GDP) per capita and medical resources. Undeveloped regions were defined as those with regional GDP lower than the median. All-cause and cardiovascular death and initial peritonitis were recorded as outcome events. Poorer PD patients or those who lived in undeveloped areas were younger and less-educated and bore a heavier burden of medical expenses. They had lower hemoglobin and serum albumin at baseline. Low income independently predicted the highest risks for all-cause or cardiovascular death and initial peritonitis compared with medium and high income. The interaction effect between individual education and regional GDP was determined. In undeveloped regions, patients with an elementary school education or lower were at significantly higher risk for all-cause death but not cardiovascular death or initial peritonitis compared with those who attended high school or had a higher diploma. Regional GDP was not associated with any outcome events. Low personal income independently influenced all-cause and cardiovascular death, and initial peritonitis in PD patients. Education level predicted all-cause death only for patients in undeveloped regions. For PD patients in these high risk situations, integrated care before dialysis and well-constructed PD training programs might be helpful.


Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study.
Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology.


Towards a formal genealogical classification of the Lezgian languages (North Caucasus): testing various phylogenetic methods on lexical data.
A lexicostatistical classification is proposed for 20 languages and dialects of the Lezgian group of the North Caucasian family, based on meticulously compiled 110-item wordlists, published as part of the Global Lexicostatistical Database project. The lexical data have been subsequently analyzed with the aid of the principal phylogenetic methods, both distance-based and character-based: Starling neighbor joining (StarlingNJ), Neighbor joining (NJ), Unweighted pair group method with arithmetic mean (UPGMA), Bayesian Markov chain Monte Carlo (MCMC), Unweighted maximum parsimony (UMP). Cognation indexes within the input matrix were marked by two different algorithms: traditional etymological approach and phonetic similarity, i.e., the automatic method of consonant classes (Levenshtein distances). Due to certain reasons (first of all, high lexicographic quality of the wordlists and a consensus about the Lezgian phylogeny among Caucasologists), the Lezgian database is a perfect testing area for appraisal of phylogenetic methods. For the etymology-based input matrix, all the phylogenetic methods, with the possible exception of UMP, have yielded trees that are sufficiently compatible with each other to generate a consensus phylogenetic tree of the Lezgian lects. The obtained consensus tree agrees with the traditional expert classification as well as some of the previously proposed formal classifications of this linguistic group. Contrary to theoretical expectations, the UMP method has suggested the least plausible tree of all. In the case of the phonetic similarity-based input matrix, the distance-based methods (StarlingNJ, NJ, UPGMA) have produced the trees that are rather close to the consensus etymology-based tree and the traditional expert classification, whereas the character-based methods (Bayesian MCMC, UMP) have yielded less likely topologies.


Market forces can boost quality, lower costs.
Competitive market forces may do more to ensure healthcare quality than government regulatory attempts. Independent research can show that healthcare quality drives profits and increases market shares. Greater market shares increase volumes, and increased volumes can lead to lower costs per case. These improvements may better position providers for payer contract negotiations, especially as payers are encouraging providers to assume more risk. Ultimately, however, a public more informed about costs and outcomes may be necessary for market forces to reduce national average costs per case.


Use and Opinions of Prescription Opioids Among Older American Adults: Sociodemographic Predictors.
This study identifies sociodemographic predictors of prescription opioid use among older adults (age 65+) during the peak decade of U.S. opioid prescription, and tests whether pain level and Medicaid coverage mediate the association between low wealth and opioid use. Predictors of prescription nonsteroidal anti-inflammatory drug (NSAID) use, and of opinions of both drug classes, are also examined. Regressions of opioid and NSAID use on sociodemographic characteristics, pain level, and insurance type were conducted using Health and Retirement Study 2004 core and 2005 Prescription Drug Study data (n = 3,721). Mediation analyses were conducted, and user opinions of drug importance, quality, and side effects were assessed. Low wealth was a strong, consistent predictor of opioid use. Both pain level and Medicaid coverage significantly, but only partially, mediated this association. Net of wealth, there were no significant associations between education and use of, or opinions of, either class of drugs. Among older American adults, the poorest are disproportionately likely to have been exposed to prescription opioid analgesics. Wealth, rather than education, drove social class differences in mid-2000s opioid use. Opioid-related policies should take into account socioeconomic contributors to opioid use, and the needs and treatment histories of chronic pain patients.


The membrane-associated transient receptor potential vanilloid channel is the central heat shock receptor controlling the cellular heat shock response in epithelial cells.
The heat shock response (HSR) is a highly conserved molecular response to various types of stresses, including heat shock, during which heat-shock proteins (Hsps) are produced to prevent and repair damages in labile proteins and membranes. In cells, protein unfolding in the cytoplasm is thought to directly enable the activation of the heat shock factor 1 (HSF-1), however, recent work supports the activation of the HSR via an increase in the fluidity of specific membrane domains, leading to activation of heat-shock genes. Our findings support the existence of a plasma membrane-dependent mechanism of HSF-1 activation in animal cells, which is initiated by a membrane-associated transient receptor potential vanilloid receptor (TRPV). We found in various non-cancerous and cancerous mammalian epithelial cells that the TRPV1 agonists, capsaicin and resiniferatoxin (RTX), upregulated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70 and Hsp90 respectively, while the TRPV1 antagonists, capsazepine and AMG-9810, attenuated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70, Hsp90, respectively. Capsaicin was also shown to activate HSF-1. These findings suggest that heat-sensing and signaling in mammalian cells is dependent on TRPV channels in the plasma membrane. Thus, TRPV channels may be important drug targets to inhibit or restore the cellular stress response in diseases with defective cellular proteins, such as cancer, inflammation and aging.


Low frequency of disease flare in patients with rheumatic musculoskeletal diseases who received SARS-CoV-2 mRNA vaccine.
Little is known about the safety of SARS-CoV-2 vaccination in patients with rheumatic musculoskeletal disease (RMD). We evaluated the occurrence of adverse events following immunization (AEFI) in RMD patients and heathy subjects who received anti-SARS-CoV-2 mRNA vaccine. We performed a telephone interview collecting any adverse event (AE) following immunization (AEFI) that occurred in RMD patients and healthy controls after the two doses of mRNA vaccine including common local reactogenicity and systemic events (for example, fever, fatigue/malaise, joint and muscle pain). We also investigated the onset of new signs or symptoms of the RMD after the vaccination. We evaluated 126 patients with RMDs [105 females and 19 males, median age 51(IQR 17)] and 85 controls [62 females and 23 males, (median age 49 (20)]. Seventy patients (55.6%) were taking immunosuppressants, conventional synthetic (n=31, 43.3%) and/or biological [TNF inhibitors (n=49, 68.6%)], and 30 (23.8%) were taking hydroxychloroquine; treatment remained unchanged in 77% of patients. Eleven out of 126 patients and none of the 85 controls previously contracted COVID-19. The median follow-up from the completion of vaccination was 15 (3) weeks both in patients and controls. We reviewed 5 suspected cases confirming mild articular flares in 3 women (2.8) with inflammatory arthritis (2 psoriatic arthritis and 1 rheumatoid arthritis) while no disease reactivation was recorded in patients with connective tissue diseases; the incidence rate of RMD reactivation was 0.007 person/month. Multivariable logistic regression analysis showed similar frequencies of local and systemic AEFI in patients and controls with no effect of therapies or previous COVID-19. Local reaction-pain in the injection site-was the most frequently reported AEFI both in RMD and controls (71% and 75% of all the AEFI, respectively) after the first dose. Overall, up to 66% of patients experienced at least one AEFI at the second dose and up to 62% in the control group. Most of AEFI occurred within 2 days of vaccine administration. Two RMD patients developed pauci-symptomatic COVID-19 after the first dose of vaccine. The low incidence rate of disease reactivation and the similar AEFI occurrence compared to controls should reassure on mRNA vaccine safety in RMD patients.


Stereotactic radiosurgery for arteriovenous malformations, Part 5: management of brainstem arteriovenous malformations.
In this paper, the authors' goal was to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the medulla, pons, and midbrain. Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 67 patients had AVMs in the brainstem. In this series, 51 patients (76%) had a prior hemorrhage. The median target volume was 1.4 cm(3) (range 0.1-13.4 cm(3)). The median margin dose was 20 Gy (range 14-25.6 Gy). Obliteration of the AVMs was eventually documented in 35 patients at a median follow-up of 73 months (range 6-269 months). The actuarial rates of documentation of total obliteration were 41%, 70%, 70%, and 76% at 3, 4, 5, and 10 years, respectively. Higher rates of AVM obliteration were associated only with a higher margin dose. Four patients (6%) suffered a hemorrhage during the latency period, and 2 patients died. The rate of AVM hemorrhage after SRS was 3.0%, 3.0%, and 5.8% at 1, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.9%. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 7 patients (10%) after SRS, and a delayed cyst developed in 2 patients (3%). One patient died at an outside institution with symptoms of AREs and unrecognized hydrocephalus. Higher 12-Gy volumes and higher Spetzler-Martin grades were associated with a higher risk of symptomatic AREs. Ten of 22 patients who had ocular dysfunction before SRS had improvement, 9 were unchanged, and 3 were worse due to AREs. Eight of 14 patients who had hemiparesis before SRS improved, 5 were unchanged, and 1 was worse. Although hemorrhage after obliteration did not occur in this series, patients remained at risk during the latency interval until obliteration occurred. Thirty-eight percent of the patients who had neurological deficits due to prior hemorrhage improved. Higher dose delivery in association with conformal and highly selective SRS is required for safe and effective radiosurgery.


In utero transplantation of fetal liver stem cells in humans.
Following 15 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The three fetuses that we treated were 28, 26, and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the third one had thalassemia major. Donor cells were obtained from 7- to 10-week-old fetuses, with conditions approved by the National Committee for Bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% than 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989 and it is too early for a thorough evaluation of the immunological effects of the transplant, although donor cell engraftment has been proven (Y chromosome in this female patient). The third patient has also evidence of donor cell take (Y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)


Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel.
Sexual dysfunction is highly prevalent in both sexes and adversely affects patients' quality of life and well being. Given the frequent association between sexual dysfunction and cardiovascular disease, in addition to the potential cardiac risk of sexual activity itself, a consensus panel was convened to develop recommendations for clinical management of sexual dysfunction in patients with cardiovascular disease. Based upon a review of the research and presentations by invited experts, a classification system was developed for stratification of patients into high, low, and intermediate categories of cardiac risk. The large majority of patients are in the low-risk category, which includes patients with (1) controlled hypertension; (2) mild, stable angina; (3) successful coronary revascularization; (4) a history of uncomplicated myocardial infarction (MI); (5) mild valvular disease; and (6) no symptoms and <3 cardiovascular risk factors. These patients can be safely encouraged to initiate or resume sexual activity or to receive treatment for sexual dysfunction. An important exception is the use of sildenafil in patients taking nitrates in any form. Patients in the intermediate-risk category include those with (1) moderate angina; (2) a recent MI (<6 weeks); (3) left ventricular dysfunction and/or class II congestive heart failure; (4) nonsustained low-risk arrhythmias; and (5) >/=3 risk factors for coronary artery disease. These patients should receive further cardiologic evaluation before restratification into the low- or high-risk category. Finally, patients in the high-risk category include those with (1) unstable or refractory angina; (2) uncontrolled hypertension; (3) congestive heart failure (class III or IV); (4) very recent MI (<2 weeks); (5) high-risk arrhythmias; (6) obstructive cardiomyopathies; and (7) moderate-to-severe valvular disease. These patients should be stabilized by specific treatment for their cardiac condition before resuming sexual activity or being treated for sexual dysfunction. A simple algorithm is provided for guiding physicians in the management of sexual dysfunction in patients with varying degrees of cardiac risk.


Correlations between brain cortical thickness and cutaneous pain thresholds are atypical in adults with migraine.
Migraineurs have atypical pain processing, increased expectations for pain, and hypervigilance for pain. Recent studies identified correlations between brain structure and pain sensation in healthy adults. The objective of this study was to compare cortical thickness-to-pain threshold correlations in migraineurs to healthy controls. We hypothesized that migraineurs would have aberrant relationships between the anatomical neurocorrelates of pain processing and pain thresholds. Pain thresholds to cutaneously applied heat were determined for 31 adult migraineurs and 32 healthy controls. Cortical thickness was determined from magnetic resonance imaging T1-weighted sequences. Regional cortical thickness-to-pain threshold correlations were determined for migraineurs and controls separately using a general linear model whole brain vertex-wise analysis. A pain threshold-by-group interaction analysis was then conducted to estimate regions where migraineurs show alterations in the pain threshold-to-cortical thickness correlations relative to healthy controls. Controls had negative correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left posterior cingulate/precuneus, right superior temporal, right inferior parietal, and left inferior temporal regions, and a negative correlation (p<0.01 Monte Carlo corrected) with a left superior temporal/inferior parietal region. Migraineurs had positive correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left superior temporal/inferior parietal, right precuneus, right superior temporal/inferior parietal, and left inferior parietal regions. Cortical thickness-to-pain threshold correlations differed between migraine and control groups (p<0.01 uncorrected) for right superior temporal/inferior parietal, right precentral, left posterior cingulate/precuneus, and right inferior parietal regions and (p<0.01 Monte Carlo corrected) for a left superior temporal/inferior parietal region. Unlike healthy control subjects who have a significant negative correlation between cortical thickness in a superior temporal/inferior parietal region with pain thresholds, migraineurs have a non-significant positive correlation between cortical thickness in a superior temporal/inferior parietal region with pain thresholds. Since this region participates in orienting and attention to painful stimuli, absence of the normal correlation might represent a migraineurs inability to inhibit pain sensation via shifting attention away from the painful stimulus.


Nurses' knowledge and skill retention following cardiopulmonary resuscitation training: a review of the literature.
This paper reports a literature review examining factors that enhance retention of knowledge and skills during and after resuscitation training, in order to identify educational strategies that will optimize survival for victims of cardiopulmonary arrest. Poor knowledge and skill retention following cardiopulmonary resuscitation training for nursing and medical staff has been documented over the past 20 years. Cardiopulmonary resuscitation training is mandatory for nursing staff and is important as nurses often discover the victims of in-hospital cardiac arrest. Many different methods of improving this retention have been devised and evaluated. However, the content and style of this training lack standardization. A literature review was undertaken using the Cumulative Index to Nursing and Allied Health Literature, MEDLINE and British Nursing Index databases and the keywords 'cardiopulmonary resuscitation', 'basic life support', 'advanced life support' and 'training'. Papers published between 1992 and 2002 were obtained and their reference lists scrutinized to identify secondary references, of these the ones published within the same 10-year period were also included. Those published in the English language that identified strategies to enhance the acquisition or retention of Cardiopulmonary resuscitation skills and knowledge were included in the review. One hundred and five primary and 157 secondary references were identified. Of these, 24 met the criteria and were included in the final literature sample. Four studies were found pertaining to cardiac arrest simulation, three to peer tuition, four to video self-instruction, three to the use of different resuscitation guidelines, three to computer-based learning programmes, two to voice-activated manikins, two to automated external defibrillators, one to self-instruction, one to gaming and the one to the use of action cards. Resuscitation training should be based on in-hospital scenarios and current evidence-based guidelines, including recognition of sick patients, and should be taught using simulations of a variety of cardiac arrest scenarios. This will ensure that the training reflects the potential situations that nurses may face in practice. Nurses in clinical areas, who rarely see cardiac arrests, should receive automated external defibrillation training and have access to defibrillators to prevent delays in resuscitation. Staff should be formally assessed using a manikin with a feedback mechanism or an expert instructor to ensure that chest compressions and ventilations are adequate at the time of training. Remedial training must be provided as often as required. Resuscitation training equipment should be made available at ward/unit level to allow self-study and practice to prevent deterioration between updates. Video self-instruction has been shown to improve competence in resuscitation. An in-hospital scenario-based video should be devised and tested to assess the efficacy of this medium in resuscitation training for nurses.


Electrochemical Reduction of CO2: A Review of Cobalt Based Catalysts for Carbon Dioxide Conversion to Fuels.
Electrochemical CO2 reduction reaction (CO2RR) provides a promising approach to curbing harmful emissions contributing to global warming. However, several challenges hinder the commercialization of this technology, including high overpotentials, electrode instability, and low Faradic efficiencies of desirable products. Several materials have been developed to overcome these challenges. This mini-review discusses the recent performance of various cobalt (Co) electrocatalysts, including Co-single atom, Co-multi metals, Co-complexes, Co-based metal-organic frameworks (MOFs), Co-based covalent organic frameworks (COFs), Co-nitrides, and Co-oxides. These materials are reviewed with respect to their stability of facilitating CO2 conversion to valuable products, and a summary of the current literature is highlighted, along with future perspectives for the development of efficient CO2RR.


Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina.
According to reports by the Ministry of Health, in the far western region of the State of Santa Catarina, there have been no reports of hantavirus pulmonary syndrome, a zoonotic disease transmitted by feces of infected rodents. A seroepidemiological study of residents of this region, was conducted, with the aim of determining the presence of hantavirus infections. A total of 340 volunteers of both genus, from the towns of Belmonte and Paraíso, were studied. The serum of these patients was collected and used to detect IgG antibodies against recombinant N protein of Araraquara hantavirus, by ELISA assay. The positive samples were then titrated and confirmed by immunofluorescence assay. This study demonstrated the presence of IgG antibodies against hantavirus N protein in 3.5% of the population. The most frequent occupation was farm worker, 81% had direct and indirect contact with rodents, 91.7% of positive cases were farm workers, indicating that the probable cause of infection occurred during barn cleaning. These antibodies are noteworthy, given that the levels of antibodies were verified in individuals whose contact with hantavirus may have occurred many years ago. This study shows the circulation of hantavirus in the region, a fact that until now, had not reported. All the serum reagents had contact with the pathogen, but did not develop pulmonary and cardiovascular syndrome. It is important to remain alert, because hantavirus is a serious and emerging disease of some relevance.