Molecular Engineering of Functional Materials for Energy and Opto-Electronic Applications.
This review presents an overview of the dedicated research directions of the Group for Molecular Engineering of Functional Materials (GMF). This includes molecular engineering aspects of sensitizers constructed from ruthenium complexes, organic molecules, porphyrins and phthalocyanines. Manipulation of organometal trihalide perovskites, and charge transporting materials for high performance perovskite solar cells and photo-detectors are also described. Controlling phosphorescence color, and quantum yields in iridium complexes by tailoring ligands for organic light emitting diodes are demonstrated. Efficient reduction of CO(2) to CO using molecular catalyst on a protected Cu(2)O photocathode, and cost-effective water-splitting cell using a high efficiency perovskite solar cell are presented.


Acantosis nigricansis associated with risk factors related to cardiovascular disease in Mexican children with obesity.
The prevalence of obesity in Mexican children has increased during the last decade, as has the risk of early onset metabolic disorders and cardiovascular disease. To determine the association ofAcantosis nigricans (AN)with dyslipidemia, high blood pressure, body mass index (BMI), and risk factors related to eating behavior in overweight and obese children. This transverse analytical study, conducted in two Mexico City primary schools, included 300 boys and girls. Information was gathered on hereditary and perinatal background. A physical examination provided data on the presence/absence of AN, blood pressure, weight and height. The BMI and Z-score were calculated. The serum concentration of glucose, cholesterol and triglycerides was quantified and the lipoprotein profile determined. The prevalence of AN was 41.7%. An association was found between ANand risk factors for cardiovascular disease, including BMI (rS 0.432; p < 0.0001), systolic and diastolic blood pressure above the 90th percentile (rS 0.231, p < 0.0001; rS 0.128, p = 0.026; respectively), hypertriglyceridemia (rS 0.156; p = 0.007), and low levels of cHDL (rS -0.160; p = 0.006). ANwas also associated with risk eating behavior, including dieting to lose weight (p = 0.004), losing control over eating (p = 0.023), and body fat percentage above the 90th percentile (χ2 = 35.1; p = 0.0001). No association was observed between ANand serum glucose concentration (rS -0.018; p = 0.759). Logistic regression analysis demonstrated an association of ANwith a low concentration of cHDL (RM: 1.726; p = 0.041) and a high percentage of body fat (> 48%) (RM: 3.591; p = 0.001). A high prevalence of ANwas found in overweight and obese children. There was an association between ANand risk factors of cardiovascular disease, including Z-score, BMI, dyslipidemia, and high blood pressure.


Analysis of the age of Panax ginseng based on telomere length and telomerase activity.
Ginseng, which is the root of Panax ginseng (Araliaceae), has been used in Oriental medicine as a stimulant and dietary supplement for more than 7,000 years. Older ginseng plants are substantially more medically potent, but ginseng age can be simulated using unscrupulous cultivation practices. Telomeres progressively shorten with each cell division until they reach a critical length, at which point cells enter replicative senescence. However, in some cells, telomerase maintains telomere length. In this study, to determine whether telomere length reflects ginseng age and which tissue is best for such an analysis, we examined telomerase activity in the main roots, leaves, stems, secondary roots and seeds of ginseng plants of known age. Telomere length in the main root (approximately 1 cm below the rhizome) was found to be the best indicator of age. Telomeric terminal restriction fragment (TRF) lengths, which are indicators of telomere length, were determined for the main roots of plants of different ages through Southern hybridization analysis. Telomere length was shown to be positively correlated with plant age, and a simple mathematical model was formulated to describe the relationship between telomere length and age for P. ginseng.


Divergent Outcomes in Cognitive-Behavioral Therapy and Pharmacotherapy for Adult Depression.
Although the average depressed patient benefits moderately from cognitive-behavioral therapy (CBT) or pharmacotherapy, some experience divergent outcomes. The authors tested frequencies, predictors, and moderators of negative and unusually positive outcomes. Sixteen randomized clinical trials comparing CBT and pharmacotherapy for unipolar depression in 1,700 patients provided individual pre- and posttreatment scores on the Hamilton Depression Rating Scale (HAM-D) and/or Beck Depression Inventory (BDI). The authors examined demographic and clinical predictors and treatment moderators of any deterioration (increase ≥1 HAM-D or BDI point), reliable deterioration (increase ≥8 HAM-D or ≥9 BDI points), extreme nonresponse (posttreatment HAM-D score ≥21 or BDI score ≥31), superior improvement (HAM-D or BDI decrease ≥95%), and superior response (posttreatment HAM-D or BDI score of 0) using multilevel models. About 5%-7% of patients showed any deterioration, 1% reliable deterioration, 4%-5% extreme nonresponse, 6%-10% superior improvement, and 4%-5% superior response. Superior improvement on the HAM-D only (odds ratio=1.67) and attrition (odds ratio=1.67) were more frequent in pharmacotherapy than in CBT. Patients with deterioration or superior response had lower pretreatment symptom levels, whereas patients with extreme nonresponse or superior improvement had higher levels. Deterioration and extreme nonresponse and, similarly, superior improvement and superior response, both occur infrequently in randomized clinical trials comparing CBT and pharmacotherapy for depression. Pretreatment symptom levels help forecast negative and unusually positive outcomes but do not guide selection of CBT versus pharmacotherapy. Pharmacotherapy may produce clinician-rated superior improvement and attrition more frequently than does CBT.


Heterogeneity in the management and outcomes of patients with acute myocardial infarction complicated by heart failure: the National Registry of Myocardial Infarction.
Heart failure (HF) is an important predictor of poor outcome after acute myocardial infarction (AMI). However, limited data exist about the clinical significance of HF in the coronary reperfusion era and the impact of its timing on hospital outcomes. The objective of this study was to determine the clinical impact of HF complicating AMI in the National Registry of Myocardial Infarction (NRMI). A secondary objective was to determine differences in demographic and clinical characteristics, treatment, and hospital death rates in patients presenting with HF compared with those developing HF after presentation. The study sample consisted of patients with AMI and without a history of HF included in the NRMI. Of 606 500 cases included from July 1, 1994 to June 30, 2000, 123 938 (20.4%) patients had HF at the time of hospital presentation and 52 220 (8.6%) developed HF thereafter. Patients with HF were older, more likely female, had more comorbidities, and were less likely to receive effective cardiac medications compared with patients without HF. The multivariable adjusted odds for in-hospital death were higher for patients with HF at presentation and thereafter (3.1 and 5.5, respectively) than those without HF. Results from this nationwide registry suggest that the incidence and hospital death rates associated with HF complicating AMI remain high. Patients developing HF after hospital admission are at even greater risk than those presenting with HF. Effective cardiac therapies remain underutilized in these patients, and the reasons for this underutilization need to be explored.


Functional source separation applied to induced visual gamma activity.
Objective of this work was to explore the performance of a recently introduced source extraction method, FSS (Functional Source Separation), in recovering induced oscillatory change responses from extra-cephalic magnetoencephalographic (MEG) signals. Unlike algorithms used to solve the inverse problem, FSS does not make any assumption about the underlying biophysical source model; instead, it makes use of task-related features (functional constraints) to estimate source/s of interest. FSS was compared with blind source separation (BSS) approaches such as Principal and Independent Component Analysis, PCA and ICA, which are not subject to any explicit forward solution or functional constraint, but require source uncorrelatedness (PCA), or independence (ICA). A visual MEG experiment with signals recorded from six subjects viewing a set of static horizontal black/white square-wave grating patterns at different spatial frequencies was analyzed. The beamforming technique Synthetic Aperture Magnetometry (SAM) was applied to localize task-related sources; obtained spatial filters were used to automatically select BSS and FSS components in the spatial area of interest. Source spectral properties were investigated by using Morlet-wavelet time-frequency representations and significant task-induced changes were evaluated by means of a resampling technique; the resulting spectral behaviours in the gamma frequency band of interest (20-70 Hz), as well as the spatial frequency-dependent gamma reactivity, were quantified and compared among methods. Among the tested approaches, only FSS was able to estimate the expected sustained gamma activity enhancement in primary visual cortex, throughout the whole duration of the stimulus presentation for all subjects, and to obtain sources comparable to invasively recorded data.


Diverse patterns of genomic targeting by transcriptional regulators in Drosophila melanogaster.
Annotation of regulatory elements and identification of the transcription-related factors (TRFs) targeting these elements are key steps in understanding how cells interpret their genetic blueprint and their environment during development, and how that process goes awry in the case of disease. One goal of the modENCODE (model organism ENCyclopedia of DNA Elements) Project is to survey a diverse sampling of TRFs, both DNA-binding and non-DNA-binding factors, to provide a framework for the subsequent study of the mechanisms by which transcriptional regulators target the genome. Here we provide an updated map of the Drosophila melanogaster regulatory genome based on the location of 84 TRFs at various stages of development. This regulatory map reveals a variety of genomic targeting patterns, including factors with strong preferences toward proximal promoter binding, factors that target intergenic and intronic DNA, and factors with distinct chromatin state preferences. The data also highlight the stringency of the Polycomb regulatory network, and show association of the Trithorax-like (Trl) protein with hotspots of DNA binding throughout development. Furthermore, the data identify more than 5800 instances in which TRFs target DNA regions with demonstrated enhancer activity. Regions of high TRF co-occupancy are more likely to be associated with open enhancers used across cell types, while lower TRF occupancy regions are associated with complex enhancers that are also regulated at the epigenetic level. Together these data serve as a resource for the research community in the continued effort to dissect transcriptional regulatory mechanisms directing Drosophila development.


Influence of transition metal doping on the electronic and optical properties of ReS2 and ReSe2 monolayers.
We investigate the structural, electronic and optical properties of transition metal doped triclinic monolayered rhenium disulfide and diselenide (ReS2 and ReSe2) by means of quantum mechanical calculations. The calculated electronic band gaps for ReS2 and ReSe2 monolayers are 1.43 eV and 1.23 eV, respectively, with both having a non-magnetic ground state. The calculated dopant substitutional energies under both Re-rich and X(S or Se)-rich conditions show that it is possible to experimentally synthesize transition metal doped ReX2 (where X is S or Se) monolayer systems. We found that the presence of dopant ions (such as V, Cr, Mn, Fe Co, Nb, Mo, Ta and W) in the ReS2 and ReSe2 monolayers significantly modifies their electronic ground states with consequent introduction of defect levels and modification of the density of states profile. However, it was found that Mn doped structures show a very minute reduction of the electronic band gap. We found that a ferro- or a non-magnetic ground state configuration was obtained depending on the choice of dopant ions in ReS2 and ReSe2 monolayers. Cr, Fe and Co doping result in a ferro-magnetic ground state configuration of the ReX2 structures. The calculated absorption and reflectivity spectra show that this class of dopants causes a general increase in the absorption spectral peaks but only a minute influence on the reflectivity. Optical anisotropy was observed depending on whether the direction of polarization in the xy-plane is either parallel or perpendicular.


Two-wavelength beam deflection technique for electron density measurements in laser-produced plasmas.
We describe the use of a two-wavelength beam deflection technique in the measurement of electron density and expansion velocity in a laser-produced plasma. Beam deflection measurements are made with a spatial resolution of 250 microm, temporal resolution of 25 ns, and a dynamic range of 1000. Several techniques for determining the spatial and temporal variation of the electron density from beam deflection measurements are described.


Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women.
To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premenstrual dysphoric disorder (PMDD). In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002. Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects. Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor. clinicaltrials.gov Identifier: NCT00620581.


Effects of extensor synovectomy and excision of the distal ulna in rheumatoid arthritis on long-term function.
Objective outcomes data after excision of the distal ulna in rheumatoid arthritis are lacking. The aim of this study was to evaluate the functional results of this surgery in the long term. We prospectively collected data on range of motion (22 wrists), visual analog pain scores (14 wrists), and grip strength measured using a Jamar dynamometer (20 hands) in a group of 23 patients (26 wrists) preoperatively and at 3 months, 12 months, and a minimum of 5 years postoperatively (range, 5.3-10.4 y). The Jebsen-Taylor hand function test was administered to 9 patients at the same time points. A subgroup of patients also underwent extensor carpi radialis longus to extensor carpi ulnaris tendon transfer (11 wrists). At one year, there were improvements in wrist pronation and supination, which were maintained at final follow-up. Active radial deviation decreased significantly at 3 months (p = .01) and one year (p = .02); this remained reduced at final follow-up (not significant). Wrist extension and active ulnar deviation showed slight improvements by one year, but reduced to levels below that measured preoperatively by final follow-up. Wrist flexion was significantly reduced at all time points postoperatively. Grip strength showed improvement from 10.0 kg (standard deviation [SD] 4.1 kg) preoperatively to 12.5 kg (SD 4.6 kg) 1 year after surgery and returned to preoperative levels (9.5 kg, SD 5.6 kg) by final follow-up. Wrist pain was significantly reduced from a mean score of 5 (SD 4) preoperatively to 2 (SD 2) postoperatively (p = .01). The Jebsen-Taylor hand function test showed improvements in writing and card turning. In the long term, excision of the distal ulna in rheumatoid patients results in an improvement in some aspects of hand function. There is a significant (p = .01) reduction in wrist pain but a reduction of wrist flexion. Therapeutic IV.


Is indomethacin harmful in spinal cord injury treatment? An experimental study.
This study was designed to analyze the effect of early indomethacin on the lipid peroxidation after spinal cord injury in rats. The use of anti-inflammatory drugs to affect delayed and secondary injury after trauma to the spinal cord has now become a matter of standard clinical practice. However, spinal cord injury remains an enormous clinical problem and research that may lead to improved treatment is to be encouraged and commended. Three experimental groups consisting of 40 rats each were formed. Using microsurgical technique, total laminectomy between T5 and T10 was performed. Spinal cord injury was achieved with an epidural aneurysm clip, and pharmacological treatment immediate after the injury was performed by injecting indomethacin intraperitoneally (i.p.) at a dose of 3 mg/kg to indomethacin-treated group. The three main groups were divided into subgroups of 8 rats each. It was planned to stop the biochemical reactions at a different time in each of these subgroups, by the application of liquid nitrogen to the spinal cord and paravertebral structures at the end of the 1st, 15th, 30th, 60th, and 90th minutes. All the spinal cords were removed and protected from further reactions by immersing in the liquid nitrogen tank. The lipid peroxidation levels were assessed by determining thiobarbituric acid reactive substances formation. The results of the study showed that the administration of 3 mg/kg indomethacin immediately after spinal cord injury induces lipid peroxidation to a significant degree (p<0.05 one-way ANOVA and Tukey HSD tests) when compared to the saline-treated group. This result suggests that early posttraumatic indomethacin treatment may be harmful in spinal cord injury.


eHealth and mHealth in prostate cancer detection and active surveillance.
eHealth and mobile health (mHealth) offer patients, healthcare providers, researchers, and policy makers new potential to improve wellness, practice prevention and reduce suffering from diseases. While the eHealth market is growing to an expected US $26 billion, its potential in the field of Urology is still underused. Research has shown that currently only 176 apps (of the 300,000 medical apps available) were found in the Apple App Store and Google Play Store, of which 20 were prostate cancer related. Three good examples of eHealth/mHealth applications are the Rotterdam Prostate Cancer Risk Calculator (RPCRC) website and app, the Prostate cancer Research International Active Surveillance (PRIAS) website and the Follow MyPSA app for men on active surveillance for prostate cancer: they are tools with a clear vision that offer true added value in daily clinical practice and which positively influence healthcare beyond borders. To increase the uptake of eHealth applications in the coming years, it is important to involve professionals in their design and development, and to guarantee the safety and privacy of its users and their data.


Immunization with antigen and interleukin 2 in vivo overcomes Ir gene low responsiveness.
We studied the effect of purified interleukin 2 (IL-2), made by recombinant DNA techniques, on the serum antibody response to myoglobin in high- and low-responder mice. Previous studies (6, 7) have shown that this response is controlled by H-2-linked Ir genes. The IL-2 was emulsified with the antigen in complete Freund's adjuvant to provide a sustained high local concentration. In low-responder B10.BR mice, a single dose (optimum 50,000 U) resulted in a consistent 10-50-fold increase in specific serum antibody throughout the time course of the response, from 10 d to 46 d after immunization. In contrast, no effect of IL-2 was seen in congenic high-responder B10.D2 mice. With IL-2, the low-responder mice achieved specific antibody levels comparable to those of high responders. Vehicle alone had no effect, and IL-2 alone, without antigen, did not induce myoglobin-specific antibody. No effect of IL-2 was seen in athymic nude mice of high-responder H-2 haplotype. The effect of IL-2 may be on a small number of responding T cells in the low responder mice, but it is possible that IL-2 also acts directly on B cells in a response that remains T-dependent, and therefore is not observed in athymic mice. We suggest that IL-2 may enhance suboptimal T cell help in the low responder, whereas help is not limiting in the high responder. This approach may enable the study of antibody responses in low responders otherwise too weak to analyze, and may be useful in producing antibodies to poorly immunogenic antigens. Potential clinical uses include immunization with weak antigens in normal patients, or with any antigen in certain immunodeficient patients.


Analysis of pediatric thrombotic patients in Turkey.
This study analyzes the data of thrombotic children who were followed up in different pediatric referral centers of Turkey, to obtain more general data on the diagnosis, risk factors, management, and outcome of thrombosis in Turkish children. A simple two-page questionnaire was distributed among contact people from each center to standardize data collection. Thirteen pediatric referral centers responded to the invitation and the total number of cases was 271. All children were diagnosed with thromboembolic disease between January 1995 and October 2001. Median age at time of first thrombotic event was 7.0 years. Of the children 4% of the cases were neonates, 12% were infants less than 1 year old, and 17% were adolescents. Thromboembolic event was mostly located in the cerebral vascular system (32%), deep venous system of the limbs, femoral and iliac veins (24%), portal veins (10%), and intracardiac region (9%). Acquired risk factors were present in 86% of the children. Infection was the most common underlying risk factor. Inherited risk factors were present in 30% of the children. FVL was the most common inherited risk factor. Acquired and inherited risk factors were present simultaneously in 19% of the patients. Eleven children had a history of familial thrombosis. Due to the local treatment preferences, the treatment of the children varied greatly. Outcome of the 142 patients (52%) was reported: 88 (62%) patients had complete resolution, 47 (33%) had complications, 12 (9%) had recurrent thrombosis, and 34 (24%) died. Three children (2.1%) died as a direct consequence of their thromboembolic disease. The significant morbidity and mortality found in this study supports the need for multicentric prospective clinical trials to obtain more generalizable data on management and outcome of thrombosis in Turkish children.


Web/Internet-based telemonitoring of a randomized controlled trial evaluating the time-integrated effects of a 24-week multicomponent intervention on key health outcomes in patients with fibromyalgia.
The aims of the study were to assess the efficacy of a multicomponent intervention and evaluate the feasibility and user acceptance of an internet-based home telemedical surveillance system for the evaluation of pain and other key health outcomes in patients with fibromyalgia (FM). The study involved 76 FM patients who were randomised to usual care or the multicomponent exercise programme, which consisted of 24 twice-weekly sessions of combined aerobic, muscle strength training exercises and education. All the patients completed the revised version of the Fibromyalgia Impact Questionnaire (FIQR) and the self-administered Fibromyalgia Activity Score (FAS). A predefined website allowed authorised users to enter data via a personal computer (PC) and Internet browser. The differences between the groups were assessed using the Mann-Whitney U-test and Fisher's exact test, and the correlations were analysed using Spearman's rank correlation test. The multicomponent intervention led to a clinically relevant difference in improvement in comparison with the standard approach. It markedly improved the FIQR symptom subscale score, significantly increased the time-integrated area under the curve (AUC) of the FAS scores, and led to a greater benefit in terms of fatigue and the quality of sleep. The mean change in the AUC of the total FIQR score closely correlated with the changes in the AUC of the total FAS score. The multicomponent approach to FM was effective in treating the key symptoms and maintaining the improvements in the short term, and telemonitoring proved to be an easyto-use solution for patient-centred data acquisition.


Effects of acute exposure to ultrahigh radiofrequency radiation on three antenna engineers.
Three men were accidentally exposed to high levels of ultrahigh frequency radiofrequency radiation (785 MHz mean frequency) while working on a television mast. They experienced an immediate sensation of intense heating of the parts of the body in the electromagnetic field followed by a variety of symptoms and signs which included pain, headache, numbness, and parasthesiae, malaise, diarrhoea, and skin erythema. The most notable problem was that of acute then chronic headache involving the part of the head which was most exposed.


Factors Affecting Venture Funding of Healthcare AI Companies.
Venture Capital (VC) funding raised by companies producing Artificial Intelligence (AI) or Machine Learning (ML) solutions is on the rise and a driver of technology development. In healthcare, VC funding is distributed unevenly and certain technologies have attracted significantly more funding than others have. We analyzed a database of 106 Healthcare AI companies collected from open online sources to understand factors affecting the VC funding of AI companies operating in different areas of healthcare. The results suggest that there is a significant connection between higher funding and having research organizations or pharmaceutical companies as the customer of the product or service. In addition, focusing on AI solutions that are applied to direct patient care delivery is associated with lower funding. We discuss the implications of our findings for public health technology funding institutions.


The electrochemical effect of various Si/Zr molar ratios on anode materials in lithium-ion batteries.
The aim of this study was to unveil the mechanisms of SiO2/ZrO2 (SSZ) anode materials through electrochemical analysis and to understand the effect of various Si/Zr molar ratios (Si/Zr = 0.5, 1, and 2) on the performance of SSZ anode materials with these mechanisms. The 2-SSZ (Si/Zr = 2) electrode had a much higher capacity than that of the 0.5- or 1-SSZ (Si/Zr = 0.5 or 1) electrode. It exhibited superior cycling performance when compared to commercial graphite (theoretical capacity of 372 mA h g-1). The 2-SSZ had a capacity of 461 mA h g-1 at a high current density of 100 mA g-1 over 30 cycles. These characteristics are due to the effects from each of the different reversible materials formed by the SSZs. Zr2Si and Zr5Si3, ZrSi, or ZrSi2 were formed by the 0.5-, 1-, and 2-SSZs, respectively, which would affect the reversible storage capacity. ZrSi2 provided an increase in the possible reaction area for the guest species (lithium ions) at the empty interstitial site in the host materials as well as a large area for accommodating a volume change. It was supportive by maintaining the lattice constant and reducing the ratio of the structure distortion. Furthermore, the 2-SSZ structure consisted of an overall amorphous structure with a crystalline structure related to the Zr-O-Si bond unlike the 0.5- and 1-SSZs which had an overall crystalline structure. Such a combined structure of 2-SSZ was advantageous for providing good capacity due to the amorphous structure and an efficient pathway for electron transport and little pulverization due to the crystalline structure. This structure led to its superior performance and long lifespan.


LCA applied to elucidate opportunities for biogas from wastewaters in Colombia.
Biogas produced in municipal and industrial wastewater treatment facilities (BWWF) is a resource wasted in several socio-economic contexts. BWWF-based projects are compared against energy projects using conventional electricity or natural gas (NG), following strict economic considerations that usually tip the balance in favour of conventional energy supply. This is because the economic gain associated with the environmental benefits of using small biogas sources like BWWF does not overcome the technical and financial effort required in these types of project. This paper shows a broader application of life cycle assessment (LCA) methodology to explore opportunities for positive (or effective) utilization of BWWF in the Colombian context. LCA has been used to evaluate the supply-chain of NG which is the direct competitor of BWWF, in three different Colombian regions, in order to identify those where higher NG environmental impacts offer increased environmental added-value to BWWF use. LCA was also applied to study two BWWF valorization scenarios in the poultry processing industry. It shows how valorization options for BWWF are more realistic and effective when specific-regional loads are applied to the environmental assessment of NG supply-chain and BWWF valorization.


Species Diversity and Invasion Resistance in a Marine Ecosystem.
Theory predicts that systems that are more diverse should be more resistant to exotic species, but experimental tests are needed to verify this. In experimental communities of sessile marine invertebrates, increased species richness significantly decreased invasion success, apparently because species-rich communities more completely and efficiently used available space, the limiting resource in this system. Declining biodiversity thus facilitates invasion in this system, potentially accelerating the loss of biodiversity and the homogenization of the world's biota.


Modulation of c-Myc activity and apoptosis in vivo.
We have developed an animal tumor model system to study the effects of c-Myc activation on apoptosis induction in vivo. Tumors were generated in SCID mice from Rat-1 fibroblasts that constitutively express an inactive c-Myc-estrogen receptor fusion protein (T.D. Littlewood et al, Nucleic Acids Res., 23: 1686 -1690, 1995), which is activated in vivo by the administration of 4-hydroxytamoxifen in time release pellets. We demonstrate that activation of c-Myc results in a substantial increase in the number of apoptotic tumor cells and that this apoptosis is predominant in regions of tumor hypoxia. c-Myc-induced apoptosis of hypoxic cells is inhibited in tumors that overexpress the human Bcl-2 protein. Bcl-2, however, does not prevent p53 protein accumulation or the down-regulation of the cyclin-cdk inhibitor p27 protein following c-Myc activation by 4-hydroxytamoxifen. This result suggests that Bcl-2 does not affect c-Myc function directly but acts downstream of c-Myc to inhibit apoptosis. We propose that the ability of activated c-Myc to enhance cellular proliferation might contribute to the genesis of early neoplasms that are held in check by the alternate ability of c-Myc to induce apoptosis of cells that have outgrown their supply of oxygen or other factors associated with hypoxic regions of solid tumors. Secondary genetic lesions downstream of c-Myc that suppress the apoptotic potential of tumor cells, such as Bcl-2 overexpression, might play an important role in the malignant progression of these tumors because they would disrupt the balance between apoptosis and proliferation initiated by c-Myc deregulation.


Does hyperglycemia downregulate glucose transporters in the brain?
Diabetes is a metabolic condition associated with hyperglycemia manifested by the elevation of blood glucose levels occurring when the pancreas decreases or stops the production of insulin, in case of insulin resistance or both. The current literature supports that insulin resistance may be responsible for the memory decline associated with diabetes. Glucose transporters (GLUTs) are a family of proteins involved in glucose transport across biological membranes. GLUT-1 and GLUT-3 are involved in glucose delivery to the brain. Evidence suggests that both transporters are downregulated in chronic peripheral hyperglycemia. Here we show the mechanisms of glucose transport and its influence on cognitive function, including a hypothesis of how peripheral hyperglycemia related genes network interactions may lead to glucose transporters downregulation and its possible consequences.


How to carry out conceptual properties norming studies as parameter estimation studies: Lessons from ecology.
Conceptual properties norming studies (CPNs) ask participants to produce properties that describe concepts. From that data, different metrics may be computed (e.g., semantic richness, similarity measures), which are then used in studying concepts and as a source of carefully controlled stimuli for experimentation. Notwithstanding those metrics' demonstrated usefulness, researchers have customarily overlooked that they are only point estimates of the true unknown population values, and therefore, only rough approximations. Thus, though research based on CPN data may produce reliable results, those results are likely to be general and coarse-grained. In contrast, we suggest viewing CPNs as parameter estimation procedures, where researchers obtain only estimates of the unknown population parameters. Thus, more specific and fine-grained analyses must consider those parameters' variability. To this end, we introduce a probabilistic model from the field of ecology. Its related statistical expressions can be applied to compute estimates of CPNs' parameters and their corresponding variances. Furthermore, those expressions can be used to guide the sampling process. The traditional practice in CPN studies is to use the same number of participants across concepts, intuitively believing that practice will render the computed metrics comparable across concepts and CPNs. In contrast, the current work shows why an equal number of participants per concept is generally not desirable. Using CPN data, we show how to use the equations and discuss how they may allow more reasonable analyses and comparisons of parameter values among different concepts in a CPN, and across different CPNs.


Fourier-transform coherent anti-Stokes Raman scattering microscopy.
We report a novel Fourier-transform-based implementation of coherent anti-Stokes Raman scattering (CARS) microscopy. The method employs a single femtosecond laser source and a Michelson interferometer to create two pulse replicas that are fed into a scanning multiphoton microscope. By varying the time delay between the pulses, we time-resolve the CARS signal, permitting easy removal of the nonresonant background while providing high resolution, spectrally resolved images of CARS modes over the laser bandwidth (approximately 1500 cm(-1)). We demonstrate the method by imaging polystyrene beads in solvent.


Cardiocerebral resuscitation is associated with improved survival and neurologic outcome from out-of-hospital cardiac arrest in elders.
Recent studies have shown that a new emergency medical services (EMS) protocol for treating patients who suffer out-of-hospital cardiac arrest (OHCA), cardiocerebral resuscitation (CCR), significantly improves survival compared to standard advanced life support (ALS). However, due to their different physiology, it is unclear if all elders, or any subsets of elders who are OHCA victims, would benefit from the CCR protocol. The objectives of this analysis were to compare survival by age group for patients receiving CCR and ALS, to evaluate their neurologic outcome, and to determine what other factors affect survival in the subset of patients who do receive CCR. An analysis was performed of 3,515 OHCAs occurring between January 2005 and September 2008 in the Save Hearts in Arizona Registry. A total of 1,024 of these patients received CCR. Pediatric patients and arrests due to drowning, respiratory, or traumatic causes were excluded. The registry included data from 62 EMS agencies, some of which instituted CCR. Outcome measures included survival to hospital discharge and cerebral performance category (CPC) scores. Logistic regression evaluated outcomes in patients who received CCR versus standard ALS across age groups, adjusted for known potential confounders, including bystander cardiopulmonary resuscitation (CPR), witnessed arrest, EMS dispatch-to-arrival time, ventricular fibrillation (Vfib), and agonal respirations on EMS arrival. Predictors of survival evaluated included age, sex, location, bystander CPR, witnessed arrest, Vfib/ventricular tachycardia (Vtach), response time, and agonal breathing, based on bivariate results. Backward stepwise selection was used to confirm predictors of survival. These predictors were then analyzed with logistic regression by age category per 10 years of age. Individuals who received CCR had better outcomes across age groups. The increase in survival for the subgroup with a witnessed Vfib was most prominent on those<40 years of age (3.7% for standard ALS patients vs. 19% for CCR patients, odds ratio [OR]=5.94, 95% confidence interval [CI]=1.82 to 19.26). This mortality benefit declined with age until the >or=80 years age group, which regained the benefit (1.8% vs. 4.6%, OR=2.56, 95% CI=1.10 to 5.97). Neurologic outcomes were also better in the patients who received CCR (OR=6.64, 95% CI=1.31 to 32.8). Within the subgroup that received CCR, the factors most predictive of improved survival included witnessed arrest, initial rhythm of Vfib/Vtach, agonal respirations upon arrival, EMS response time, and age. Neurologic outcome was not adversely affected by age. Cardiocerebral resuscitation is associated with better survival from OHCA in most age groups. The majority of patients in all age groups who survived to hospital discharge and who could be reached for follow-up had good neurologic outcome. Among patients receiving CCR for OHCA, witnessed arrest, Vfib/Vtach, agonal respirations, and early response time are significant predictors of survival, and these do not change significantly based on age.


Cytotoxicity and genotoxicity of size-fractionated iron oxide (magnetite) in A549 human lung epithelial cells: role of ROS, JNK, and NF-κB.
Airborne particulate matter (PM) of varying size and composition is known to cause health problems in humans. The iron oxide Fe(3)O(4) (magnetite) may be a major anthropogenic component in ambient PM and is derived mainly from industrial sources. In the present study, we have investigated the effects of four different size fractions of magnetite on signaling pathways, free radical generation, cytotoxicity, and genotoxicity in human alveolar epithelial-like type-II cells (A549). The magnetite particles used in the exposure experiments were characterized by mineralogical and chemical techniques. Four size fractions were investigated: bulk magnetite (0.2-10 μm), respirable fraction (2-3 μm), alveolar fraction (0.5-1.0 μm), and nanoparticles (20-60 nm). After 24 h of exposure, the A549 cells were investigated by transmission electron microscopy (TEM) to study particle uptake. TEM images showed an incorporation of magnetite particles in A549 cells by endocytosis. Particles were found as agglomerates in cytoplasm-bound vesicles, and few particles were detected in the cytoplasm but none in the nucleus. Increased production of reactive oxygen species (ROS), as determined by the 2',7'-dichlorfluorescein-diacetate assay (DCFH-DA), as well as genotoxic effects, as measured by the cytokinesis block-micronucleus test and the Comet assay, were observed for all of the studied fractions after 24 h of exposure. Moreover, activation of c-Jun N-terminal kinases (JNK) without increased nuclear factor kappa-B (NF-κB)-binding activity but delayed IκB-degradation was observed. Interestingly, pretreatment of cells with magnetite and subsequent stimulation with the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) led to a reduction of NF-κB DNA binding compared to that in stimulation with TNFα alone. Altogether, these experiments suggest that ROS formation may play an important role in the genotoxicity of magnetite in A549 cells but that activation of JNK seems to be ROS-independent.


Managing hereditary angioedema patients undergoing otolaryngeal procedures.
Hereditary angioedema (HAE), a rare autosomal dominant disorder, is characterized by repeated attacks of swelling of the skin, gastrointestinal tract, face, larynx, and other organs. In most cases it is caused by low levels of functional C1 esterase inhibitor (C1-INH), a serine protease inhibitor that plays important regulatory roles in the complement, contact, and fibrinolytic pathways. Lack of functional C1-INH results in excessive release of bradykinin, which triggers vasodilation, vascular permeability, and edema. Most attacks are mild and self-limiting, but untreated laryngeal attacks may cause rapid asphyxiation and death. Potential triggers of laryngeal attacks include trauma to or manipulation of the face, mouth, or upper airway. Therefore, before performing such a procedure in a patient with HAE, the otolaryngologist should consult with the patient, the physician managing the HAE, and the anesthesiologist and make appropriate preparations for prevention and/or treatment of an attack. Current World Allergy Organization and European guidelines recommend the use of i.v. plasma-derived C1-INH replacement for short-term prophylaxis of angioedema attacks. Other effective options include danazol given for several days before and after the procedure and fresh-frozen plasma, but these may not be as effective as C1-INH and may be associated with a high rate of adverse events. Acute attacks, which may occur many hours after a procedure, may be treated with C1-INH; icatibant, a bradykinin B2-receptor antagonist; or ecallantide, a kallikrein inhibitor, all of which have been shown to reduce the duration and severity of HAE attacks.


Reducing a cost of traumatic insemination: female bedbugs evolve a unique organ.
The frequent wounding of female bedbugs (Cimex lectularius: Cimicidae) during copulation has been shown to decrease their fitness, but how females have responded to this cost in evolutionary terms is unclear. The evolution of a unique anatomical structure found in female bedbugs, the spermalege, into which the male's intromittent organ passes during traumatic insemination, is a possible counteradaptation to harmful male traits. Several functions have been proposed for this organ, and we test two hypotheses related to its role in sexual conflict. We examine the hypotheses that the spermalege functions to (i) defend against pathogens introduced during traumatic insemination; and (ii) reduce the costs of wound healing during traumatic insemination. Our results support the 'defence against pathogens' hypothesis, suggesting that the evolution of this unique cimicid organ resulted, at least partly, from selection to reduce the costs of mating-associated infection. We found no evidence that the spermalege reduces the costs of wound healing.


American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Foundation Guide to Enhance Otologic and Neurotologic Care During the COVID-19 Pandemic.
: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.


Social jetlag, obesity and metabolic disorder: investigation in a cohort study.
Obesity is one of the leading causes of preventable death worldwide. Circadian rhythms are known to control both sleep timing and energy homeostasis, and disruptions in circadian rhythms have been linked with metabolic dysfunction and obesity-associated disease. In previous research, social jetlag, a measure of chronic circadian disruption caused by the discrepancy between our internal versus social clocks, was associated with elevated self-reported body mass index, possibly indicative of a more generalized association with obesity and metabolic dysfunction. We studied participants from the population-representative Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was associated with clinically assessed measurements of metabolic phenotypes and disease indicators for obesity-related disease, specifically, indicators of inflammation and diabetes. Our analysis was restricted to N=815 non-shift workers in our cohort. Among these participants, we found that social jetlag was associated with numerous clinically assessed measures of metabolic dysfunction and obesity. We distinguished between obese individuals who were metabolically healthy versus unhealthy, and found higher social jetlag levels in metabolically unhealthy obese individuals. Among metabolically unhealthy obese individuals, social jetlag was additionally associated with elevated glycated hemoglobin and an indicator of inflammation. The findings are consistent with the possibility that 'living against our internal clock' may contribute to metabolic dysfunction and its consequences. Further research aimed at understanding that the physiology and social features of social jetlag may inform obesity prevention and have ramifications for policies and practices that contribute to increased social jetlag, such as work schedules and daylight savings time.


Reliability of the PEDro scale for rating quality of randomized controlled trials.
Assessment of the quality of randomized controlled trials (RCTs) is common practice in systematic reviews. However, the reliability of data obtained with most quality assessment scales has not been established. This report describes 2 studies designed to investigate the reliability of data obtained with the Physiotherapy Evidence Database (PEDro) scale developed to rate the quality of RCTs evaluating physical therapist interventions. In the first study, 11 raters independently rated 25 RCTs randomly selected from the PEDro database. In the second study, 2 raters rated 120 RCTs randomly selected from the PEDro database, and disagreements were resolved by a third rater; this generated a set of individual rater and consensus ratings. The process was repeated by independent raters to create a second set of individual and consensus ratings. Reliability of ratings of PEDro scale items was calculated using multirater kappas, and reliability of the total (summed) score was calculated using intraclass correlation coefficients (ICC [1,1]). The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters. The ICC for the total score was.56 (95% confidence interval=.47-.65) for ratings by individuals, and the ICC for consensus ratings was.68 (95% confidence interval=.57-.76). The reliability of ratings of PEDro scale items varied from "fair" to "substantial," and the reliability of the total PEDro score was "fair" to "good."


DNA damage sensors ATM, ATR, DNA-PKcs, and PARP-1 are dispensable for human immunodeficiency virus type 1 integration.
Integration of a DNA copy of the viral RNA genome is a crucial step in the life cycle of human immunodeficiency virus type 1 (HIV-1) and other retroviruses. While the virally encoded integrase is key to this process, cellular factors yet to be characterized are suspected to participate in its completion. DNA damage sensors such as ATM (ataxia-telangiectasia mutated), ATR (ATM- and Rad3-related), DNA-PK (DNA-dependent protein kinase), and PARP-1 [poly(ADP-ribose) polymerase 1] play central roles in responses to various forms of DNA injury and as such could facilitate HIV integration. To test this hypothesis, we examined the susceptibility to infection with wild-type HIV-1 and to transduction with a vesicular stomatitis virus G protein (VSV-G)-pseudotyped HIV-1-derived lentiviral vector of human cells stably expressing small interfering RNAs against ATM, ATR, and PARP-1. We found that integration normally occurred in these knockdown cells. Similarly, the VSV-G-pseudotyped HIV-1-based vector could effectively transduce ATM and PARP-1 knockout mouse cells as well as human cells deficient for DNA-PK. Finally, treatment of target cells with the ATM and ATR inhibitors caffeine and wortmannin was without effect in these infectivity assays. We conclude that the DNA repair enzymes ATM, ATR, DNA-PKcs, and PARP-1 are not essential for HIV-1 integration.


Arsenic contamination of natural waters in San Juan and La Pampa, Argentina.
Arsenic (As) speciation in surface and groundwater from two provinces in Argentina (San Juan and La Pampa) was investigated using solid phase extraction (SPE) cartridge methodology with comparison to total arsenic concentrations. A third province, Río Negro, was used as a control to the study. Strong cation exchange (SCX) and strong anion exchange (SAX) cartridges were utilised in series for the separation and preservation of arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MA(V)) and dimethylarsinic acid (DMA(V)). Samples were collected from a range of water outlets (rivers/streams, wells, untreated domestic taps, well water treatment works) to assess the relationship between total arsenic and arsenic species, water type and water parameters (pH, conductivity and total dissolved solids, TDS). Analysis of the waters for arsenic (total and species) was performed by inductively coupled plasma mass spectrometry (ICP-MS) in collision cell mode. Total arsenic concentrations in the surface and groundwater from Encon and the San José de Jáchal region of San Juan (north-west Argentina within the Cuyo region) ranged from 9 to 357 μg l(-1) As. Groundwater from Eduardo Castex (EC) and Ingeniero Luiggi (LU) in La Pampa (central Argentina within the Chaco-Pampean Plain) ranged from 3 to 1326 μg l(-1) As. The pH range for the provinces of San Juan (7.2-9.7) and La Pampa (7.0-9.9) are in agreement with other published literature. The highest total arsenic concentrations were found in La Pampa well waters (both rural farms and pre-treated urban sources), particularly where there was high pH (typically > 8.2), conductivity (>2,600 μS cm(-1)) and TDS (>1,400 mg l(-1)). Reverse osmosis (RO) treatment of well waters in La Pampa for domestic drinking water in EC and LU significantly reduced total arsenic concentrations from a range of 216-224 μg l(-1) As to 0.3-0.8 μg l(-1) As. Arsenic species for both provinces were predominantly As(III) and As(V). As(III) and As(V) concentrations in San Juan ranged from 4-138 μg l(-1) to <0.02-22 μg l(-1) for surface waters (in the San José de Jáchal region) and 23-346 μg l(-1) and 0.04-76 μg l(-1) for groundwater, respectively. This translates to a relative As(III) abundance of 69-100% of the total arsenic in surface waters and 32-100% in groundwater. This is unexpected because it is typically thought that in oxidising conditions (surface waters), the dominant arsenic species is As(V). However, data from the SPE methodology suggests that As(III) is the prevalent species in San Juan, indicating a greater influence from reductive processes. La Pampa groundwater had As(III) and As(V) concentrations of 5-1,332 μg l(-1) and 0.09-592 μg l(-1) for EC and 32-242 μg l(-1) and 30-277 μg l(-1) As for LU, respectively. Detectable levels of MA(V) were reported in both provinces up to a concentration of 79 μg l(-1) (equating to up to 33% of the total arsenic). Previously published literature has focused primarily on the inorganic arsenic species, however this study highlights the potentially significant concentrations of organoarsenicals present in natural waters. The potential for separating and preserving individual arsenic species in the field to avoid transformation during transport to the laboratory, enabling an accurate assessment of in situ arsenic speciation in water supplies is discussed.


Helicobacter pylori infection in a pig model is dominated by Th1 and cytotoxic CD8+ T cell responses.
Helicobacter pylori infection is the leading cause for peptic ulcer disease and gastric adenocarcinoma. Mucosal T cell responses play an important role in mediating H. pylori-related gastric immunopathology. While induced regulatory T (iTreg) cells are required for chronic colonization without disease, T helper 1 (Th1) effector responses are associated with lower bacterial loads at the expense of gastric pathology. Pigs were inoculated with either H. pylori strain SS1 or J99. Phenotypic and functional changes in peripheral blood mononuclear cell (PBMC) populations were monitored weekly, and mucosal immune responses and bacterial loads were assessed up to 2 months postinfection. Both H. pylori strains elicited a Th1 response characterized by increased percentages of CD4(+)Tbet(+) cells and elevated gamma interferon (IFN-γ) mRNA in PBMCs. A subset of CD8(+) T cells expressing Tbet and CD16 increased following infection. Moreover, a significant increase in perforin and granzyme mRNA expression was observed in PBMCs of infected pigs, indicating a predominant cytotoxic immune response. Infiltration of B cells, myeloid cells, T cells expressing Treg- and Th17-associated transcription factors, and cytotoxic T cells was found in the gastric lamina propria of both infected groups. Interestingly, based on bacterial reisolation data, strain SS1 showed greater capacity to colonize and/or persist in the gastric mucosa than did strain J99. This novel pig model of infection closely mimics human gastric pathology and presents a suitable avenue for studying effector and regulatory responses toward H. pylori described in humans.


Effect of alkaline pH and associated Zn on the concentration and total uptake of Cd by lettuce: comparison with predictions from the CLEA model.
An eight-fold underestimate of the potential Cd exposure to humans via ingestion of lettuce grown in moderately alkaline soil has been measured experimentally. Current models of Cd uptake by leafy vegetables, which are used in risk assessment (e.g. CLEA in UK) predict higher concentration factors in acid than in alkaline soils. Experimental evidence shows that Cd uptake, although it decreases with increasing pH from acid to neutral soils, increases again in alkaline soils, confirming recent finding from other workers. The concentration of Zn in the soil also significantly affects the uptake of Cd, although this is not included in the current prediction models either. The effect of Zn on the uptake of Cd by plants is greater in slightly alkaline soils (pH 7.7) than in slightly acidic or neutral soils. High concentrations of Zn in soil (1000 mg/kg), which are often associated with elevated Cd levels, further increase the Cd concentration factor to values 12 times higher than that predicted by the CLEA model. This is due in part to the effect of the high soil Zn on reducing the above-ground biomass of the plants.


Cimetidine administration and tubular creatinine secretion in patients with compensated cirrhosis.
Cimetidine inhibits the tubular secretion of creatinine, without altering the glomerular filtration rate (GFR). During cimetidine administration the creatinine/inulin clearance ratio approaches unity in patients with renal failure. We determined the clearance of lithium (an index of fluid delivery to the distal nephron), inulin (a measure of the actual GFR) and creatinine during cimetidine administration to investigate the occurrence of tubular creatinine secretion in patients with compensated cirrhosis. A total of 12 patients with Child-Pugh A cirrhosis were studied initially. The subjects consumed a stable diet containing 100 mmol of sodium. On successive days, 9 h creatinine clearances were measured, first without and then with the oral administration of cimetidine (400 mg as a priming dose, followed by 200 mg every 3 h). During the first study day, 4 h renal lithium clearance was also calculated. A further group of five patients with fully compensated cirrhosis underwent the measurement (on successive days) of plasma inulin clearance, first without and then with the oral administration of cimetidine (same schedule of drug administration). Cimetidine administration unmasked a marked overestimation of GFR when calculated as creatinine clearance (baseline, 138+/-20 ml/min; +cimetidine, 89+/-13 ml/min; P<0.01). Consequently, during cimetidine administration the calculated lithium fractional excretion (a measure of the fraction of filtered sodium load that is delivered to the loop of Henle) rose from 21.4+/-13.2% to 32.3+/-18.9% (P<0.05), and the ratio between absolute distal tubular sodium reabsorption and filtered sodium load rose from 20.6+/-13.1% to 31.6+/-19.3% (P<0.01). Cimetidine caused no significant decrease in the actual GFR (i.e. inulin clearance) when administered to the second group of patients with compensated cirrhosis. Our data demonstrate significant tubular secretion of creatinine in patients with compensated cirrhosis and, consequently, a marked overestimation of GFR and filtered sodium load and an underestimation of the fractional distal tubular sodium reabsorption when these parameters are calculated by means of the traditional creatinine and lithium clearance computation. The true GFR (measured as inulin clearance) is unaffected by cimetidine administration.


Effects of Metformin on Spatial and Verbal Memory in Children with ASD and Overweight Associated with Atypical Antipsychotic Use.
Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use. We studied the effects of metformin (Riomet®) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management. Phase 1 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group comparison of metformin (500-850 mg given twice a day) versus placebo. During Phase 2, all participants took open-label metformin from week 17 through week 32. We assessed spatial and verbal memory using the Neuropsychological Assessment 2nd Edition (NEPSY-II) and a modified children's verbal learning task. No measures differed between participants randomized to metformin versus placebo, at either 16 or 32 weeks, after adjustment for multiple comparisons. Sixteen-week change in memory for spatial location on the NEPSY-II was nominally better among participants randomized to placebo. However, patterns of treatment response across all measures revealed no systematic differences in performance, suggesting that metformin had no effect on spatial or verbal memory in these children. Although further study is needed to support these null effects, the overall impression is that metformin does not affect memory in overweight youth with ASD who were taking atypical antipsychotic medications.


Contrasting mitochondrial diversity of European starlings (Sturnus vulgaris) across three invasive continental distributions.
European starlings (Sturnus vulgaris) represent one of the most widespread and problematic avian invasive species in the world. Understanding their unique population history and current population dynamics can contribute to conservation efforts and clarify evolutionary processes over short timescales. European starlings were introduced to Central Park, New York in 1890, and from a founding group of about 100 birds, they have expanded across North America with a current population of approximately 200 million. There were also multiple introductions in Australia in the mid-19th century and at least one introduction in South Africa in the late 19th century. Independent introductions on these three continents provide a robust system to investigate invasion genetics. In this study, we compare mitochondrial diversity in European starlings from North America, Australia, and South Africa, and a portion of the native range in the United Kingdom. Of the three invasive ranges, the North American population shows the highest haplotype diversity and evidence of both sudden demographic and spatial expansion. Comparatively, the Australian population shows the lowest haplotype diversity, but also shows evidence for sudden demographic and spatial expansion. South Africa is intermediate to the other invasive populations in genetic diversity but does not show evidence of demographic expansion. In previous studies, population genetic structure was found in Australia, but not in South Africa. Here we find no evidence of population structure in North America. Although all invasive populations share haplotypes with the native range, only one haplotype is shared between invasive populations. This suggests these three invasive populations represent independent subsamples of the native range. The structure of the haplotype network implies that the native-range sampling does not comprehensively characterize the genetic diversity there. This study represents the most geographically widespread analysis of European starling population genetics to date.


Neotropical Andes hot springs harbor diverse and distinct planktonic microbial communities.
Microbial explorations of hot springs have led to remarkable discoveries and improved our understanding of life under extreme conditions. The Andean Mountains harbor diverse habitats, including an extensive chain of geothermal heated water sources. In this study, we describe and compare the planktonic microbial communities present in five high-mountain hot springs with distinct geochemical characteristics, at varying altitudes and geographical locations in the Colombian Andes. The diversity and structure of the microbial communities were assessed by pyrosequencing the V5 - V6 region of the 16S rRNA gene. The planktonic communities varied in terms of diversity indexes and were dominated by the bacterial phyla Proteobacteria, Aquificae, Chloroflexi, Cyanobacteria, Firmicutes, Nitrospirae, and Thermotogae, with site-specific bacterial taxa also observed in some cases. Statistical analyses showed that these microbial communities were distinct from one another and that they clustered in a manner consistent with physicochemical parameters of the environment sampled. Multivariate analysis suggested that pH and sulfate were among the main variables influencing population structure and diversity. The results show that despite their geographical proximity and some shared geochemical characteristics, there were few shared operational taxonomic units (OTUs) and that community structure was influenced mainly by environmental factors that have resulted in different microbial populations.


Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme.
To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment. This prospective, observational study included 414 alcohol-dependent patients, hospitalised for a period of 3 weeks. QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36. The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated. The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge; the lowest scores being observed for social functioning and role limitations due to emotional problems. At discharge, the mean scores per dimension were similar to those observed in the French general population. Female gender, age > 45 years, living alone, working as a labourer or employee, somatic comorbidity, and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission; psychiatric comorbidity, the presence of at least five DSM-IV dependence criteria, smoking and suicidality were associated with a low Mental Component Summary score on admission. The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low. Apart from the initial score, the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs. QoL improvement after a residential treatment was related to low QoL scores at admission. Improvement in physical component of QoL was related to baseline alcohol intake and good somatic status. Improvement in mental component of QoL was related to other drugs abuse/dependence.


Karyotype versus microarray testing for genetic abnormalities after stillbirth.
Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants. The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery. In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies. Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).


Adhesion of endodontic sealers: scanning electron microscopy and energy dispersive spectroscopy.
The microscopic details of the debonded interfaces between endodontic sealers and dentin or gutta-percha were assessed in this study. Dentin, conditioned with 37% H3PO4 for 30 s, 25% citric acid for 30 s, 17% EDTA for 5 min, or a rinse with 10 ml of distilled H2O (control), and gutta-percha surfaces were coated with freshly mixed sealer: Grossman's sealer, Apexit, Ketac-Endo, AH Plus, RoekoSeal Automix, or RoekoSeal Automix with an experimental primer. The surfaces were pressed together and the sealers were allowed to set. After tensile bond strength testing, the morphological aspects of the fractured surfaces were assessed by scanning electron microscopy and energy dispersive spectroscopy. The energy dispersive spectroscopy successfully traced sealer components to the debonded surfaces. Some of the sealers penetrated into the dentinal tubules when the dentin surface had been pretreated with acids. However, these sealer tags remained occluding the tubules after bond failure in some instances only (Grossman's sealer, RoekoSeal Automix with an experimental primer, AH Plus/EDTA). Penetration of the endodontic sealers into the dentinal tubules when the smear layer was removed was not associated with higher bond strength.


Workflows for microarray data processing in the Kepler environment.
Microarray data analysis has been the subject of extensive and ongoing pipeline development due to its complexity, the availability of several options at each analysis step, and the development of new analysis demands, including integration with new data sources. Bioinformatics pipelines are usually custom built for different applications, making them typically difficult to modify, extend and repurpose. Scientific workflow systems are intended to address these issues by providing general-purpose frameworks in which to develop and execute such pipelines. The Kepler workflow environment is a well-established system under continual development that is employed in several areas of scientific research. Kepler provides a flexible graphical interface, featuring clear display of parameter values, for design and modification of workflows. It has capabilities for developing novel computational components in the R, Python, and Java programming languages, all of which are widely used for bioinformatics algorithm development, along with capabilities for invoking external applications and using web services. We developed a series of fully functional bioinformatics pipelines addressing common tasks in microarray processing in the Kepler workflow environment. These pipelines consist of a set of tools for GFF file processing of NimbleGen chromatin immunoprecipitation on microarray (ChIP-chip) datasets and more comprehensive workflows for Affymetrix gene expression microarray bioinformatics and basic primer design for PCR experiments, which are often used to validate microarray results. Although functional in themselves, these workflows can be easily customized, extended, or repurposed to match the needs of specific projects and are designed to be a toolkit and starting point for specific applications. These workflows illustrate a workflow programming paradigm focusing on local resources (programs and data) and therefore are close to traditional shell scripting or R/BioConductor scripting approaches to pipeline design. Finally, we suggest that microarray data processing task workflows may provide a basis for future example-based comparison of different workflow systems. We provide a set of tools and complete workflows for microarray data analysis in the Kepler environment, which has the advantages of offering graphical, clear display of conceptual steps and parameters and the ability to easily integrate other resources such as remote data and web services.


The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data.
The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13,835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case-Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.


Antioxidative and antiphotoaging activities of neferine upon UV-A irradiation in human dermal fibroblasts.
Our daily exposure to ultraviolet radiation (UVR) results in the production of reactive oxygen species (ROS), lipids, proteins and DNA damage and alteration in fibroblast structure, thus contributing to skin photoaging. For this reason, the use of natural bioactive compounds with antioxidant activity could be a strategic tool to overcome ultraviolet A (UV-A) induced deleterious effect. Neferine is an alkaloid extract from the seed embryos of lotus (Nelumbo nucifera Gaertn). In the present study, we report the protective effect of neferine against UV-A induced oxidative stress and photoaging in human dermal fibroblasts (HDFs). HDFs subjected to UV-A irradiation showed increased production of ROS and malondialdehyde (MDA). Furthermore, it depleted the cellular enzymatic antioxidant superoxide dismutase (SOD) and non-enzymatic antioxidant glutathione peroxidase (GPx). On the other hand, HDFs treated with neferine followed by UV-A irradiation reversed the process, reduced the ROS and lipid peroxidation and restored the antioxidants pool. Moreover, neferine treatment significantly inhibited UV-A induced matrix metalloproteinase-1 (MMP-1) expression in HDFs. Remarkable morphological and ultrastructural alterations observed in HDFs upon UV-A irradiation, were also reduced with neferine treatment. Taken together, our results suggest that neferine has strong antioxidative and photoprotective properties and thus may be a potential agent for the prevention and treatment of UV-A mediated skin photoaging.


Vitamin and mineral supplement use is associated with reduced risk of prostate cancer.
This population-based, case-control study in King County, Washington examined supplement use in 697 incident prostate cancer cases (ages 40-64) identified from the Puget Sound Surveillance, Epidemiology and End Results program registry and 666 controls recruited from the same overall population using random-digit dialing sampling. Participants reported their frequency of use of three types of multivitamins and single supplements of vitamins A, C, and E, calcium, iron, and zinc over the 2 years before diagnosis. Logistic regression analyses controlled for age, race, education, family history of prostate cancer, body mass index, number of prostate-specific antigen tests in the previous 5 years, and dietary fat intake. Adjusted odds ratios (95% confidence limits) for the contrast of > or =7/week versus no use were as follows: multivitamins, 0.96 (0.73, 1.26); vitamin A, 0.59 (0.32, 1.06); vitamin C, 0.77 (0.57, 1.04); vitamin E, 0.76 (0.54, 1.08); calcium, 1.04 (0.61, 1.78); iron, 0.50 (0.13, 1.76); and zinc, 0.55 (0.30, 1.00). Odds ratios differed little when cases were stratified by stage of disease at diagnosis or by histopathological grade. There were significant dose-response effects for zinc and ordered dose-response trends for vitamins C and E. Overall, these results suggest that multivitamin use is not associated with prostate cancer risk, but use of individual supplements of zinc, vitamin C, and vitamin E may be protective. Further study is needed to investigate the direct role of these dietary supplements, as well as the role of lifestyle variables associated with supplement use, on prostate cancer risk.


Degradation of polycyclic aromatic hydrocarbons by free and nanoclay-immobilized manganese peroxidase from Anthracophyllum discolor.
Manganese peroxidase (MnP) produced by Anthracophyllum discolor, a Chilean white rot fungus, was immobilized on nanoclay obtained from volcanic soil and its ability to degrade polycyclic aromatic hydrocarbons (PAHs) compared with the free enzyme was evaluated. At the same time, nanoclay characterization was performed. Nanoclay characterization by transmission electronic microscopy showed a particle average size smaller than 100 nm. The isoelectric points (IEP) of nanoclay and MnP from A. discolor were 7.0 and 3.7, respectively, as determined by micro electrophoresis migration and preparative isoelectric focusing. Results indicated that 75% of the enzyme was immobilized on the nanoclay through physical adsorption. As compared to the free enzyme, immobilized MnP from A. discolor achieved an improved stability to temperature and pH. The activation energy (Ea) value for immobilized MnP (51.9 kJ mol(-1)) was higher than that of the free MnP (34.4 kJ mol(-1)). The immobilized enzyme was able to degrade pyrene (>86%), anthracene (>65%), alone or in mixture, and to a less extent fluoranthene (<15.2%) and phenanthrene (<8.6%). Compared to free MnP from A. discolor, the enzyme immobilized on nanoclay enhanced the enzymatic transformation of anthracene in soil. Overall results indicate that nanoclay, a carrier of natural origin, is a suitable support material for MnP immobilization. In addition, immobilized MnP shows an increased stability to high temperature, pH and time storage, as well as an enhanced PAHs degradation efficiency in soil. All these characteristics may suggest the possible use of nanoclay-immobilized MnP from A. discolor as a valuable option for in situ bioremediation purposes.


The "pro-drug" RibCys decreases the mutagenicity of high-LET radiation in cultured mammalian cells.
We are carrying out studies aimed at reducing the mutagenic effects of high-LET 56Fe ions and 12C ions (56Fe ions, 143 keV/microm; 12C ions, 100 keV/microm) with certain drugs, including RibCys [2-(R,S)-D-ribo-(1',2',3',4'-tetrahydroxybutyl)-thiazolidine-4(R)-carboxylic acid]. RibCys, formed by condensation of L-cysteine with D-ribose, is designed so that the sulfhydryl amino acid L-cysteine is released intracellularly through nonenzymatic ring opening and hydrolysis leading to increased levels of glutathione (GSH). RibCys (4 or 10 mM), which was present during irradiation and for a few hours after, significantly decreased the yield of CD59- mutants induced by radiation in AL human-hamster hybrid cells. RibCys did not affect the clonogenic survival of irradiated cells, nor was it mutagenic itself. These results, together with the minimal side effects reported in mice and pigs, indicate that RibCys may be useful, perhaps even when used prophylactically, in reducing the mutation load created by high-LET radiation in astronauts or other exposed individuals.


Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses.


Hyperaggregating effect of hydroxyethyl starch components and University of Wisconsin solution on human red blood cells: a risk of impaired graft perfusion in organ procurement?
The standard preservation solution used during organ procurement and preservation of most organs is the University of Wisconsin (UW) solution. Despite its superiority over other cold storage solutions, the inclusion of hydroxyethyl starch (HES) as one of the components of the UW solution has been both advocated and denied. This study determined whether HES had any effect on red blood cell (RBC) aggregability and correlated aggregation parameters with HES molecular weight. Human RBC aggregability and deformability were investigated in vitro, at 4 degrees C, with a laser-assisted optical rotation cell analyzer. The study of RBC aggregation in a binary HES-HES system gave an indication about the nature of HES-RBCs interactions. Bright field microscopy and atomic force microscopy were used to morphologically characterize the aggregates size and form. High molecular weight HES and UW solution had a potent hyperaggregating effect; low molecular weight HES had a hypoaggregating effect on RBC. RBC aggregates were of large size and their resistance to dissociation by flow-induced shear stress was high. The authors' in vitro experiments conclusively showed that the physiologic function of RBCs to form aggregates is significantly affected in the presence of HES. The use of high molecular weight HES in UW solution accounts for extended and accelerated aggregation of erythrocytes that may result in stasis of blood and incomplete washout of donor organs before transplantation.


An update on prevention of venous thromboembolism in hospitalized acutely ill medical patients.
Both the recently updated consensus guidelines published by the American College of Chest Physicians, and the International Union of Angiology recommend thromboprophylaxis with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in medical patients at risk of VTE. However, no guidance is given regarding the appropriate dosing regimens that should be used for thromboprophylaxis in this patient group. LMWH (enoxaparin and dalteparin) and UFH have been shown to be effective for thromboprophylaxis in at-risk hospitalized medical patients. Although LMWH once daily (o.d.) has been shown to be as effective as UFH three times daily (t.i.d.) for thromboprophylaxis in at-risk medical patients, there are no data to show that UFH twice daily (b.i.d) is as effective as either LMWH o.d. or UFH t.i.d. On the basis of currently available evidence, the LMWHs enoxaparin and dalteparin are more attractive alternatives to UFH for the prevention of VTE in hospitalized medical patients because of their convenient once-daily administration and better safety profile, demonstrated in terms of reduced bleeding, HIT, and other adverse events.


Effect of 43 degrees treatment on expression of heat shock proteins 105, 70 and 60 in cultured monkey Sertoli cells.
To examine the possible effect of heat treatment on expression of heat shock proteins (Hsps) 105, 70, and 60 in primary monkey Sertoli cells and to evaluate the possible signal pathways. Western blot analysis, real-time polymerase chain reaction (PCR), and confocal immunohistochemistry were used to analyze mRNA and protein levels of the Hsps in response to 43 degrees treatment of Sertoli cells isolated from pubertal monkey testes. Staining with Hoechst 33342 indicated Sertoli cells did not undergo apoptosis after heat treatment. Hsp105 was expressed in cytoplasm of untreated Sertoli cells. Both Hsp105 mRNA and protein levels were increased approximately 20-fold compared to those of the untreated controls at 12 h after heat treatment. Untreated Sertoli cells did not express Hsp70, but heat stress induced its expression in the cell cytoplasm. The time-course of changes in Hsp70 was similar to that of Hsp105. In contrast to Hsp105 and Hsp70, the change in Hsp60 expression was much less obvious. The protein level between 12 h and 48 h after heat treatment was only approximately 1.5-fold that of the untreated control. Extracellular regulated kinase (ERK) 1/2 inhibitor (U0126) or phosphoinositide kinase-3 (PI3K) inhibitor (LY294002) could partially block the response of Hsp105 and Hsp70 induced by heat treatment. These results indicate that the heat-induced expression of the three types of Hsp in monkey Sertoli cells might be regulated by ERK and/or PI3K signal pathways, but the profile of their expression is different, suggesting that they might have different regulatory functions in Sertoli cells.


Work-related disease in general practice: a systematic review.
The objective was to answer the following questions: What is the prevalence of potentially work-related diseases in the general practice population? What is the incidence of consulting a GP for a potentially work-related disease? What is the relationship between diseases seen in general practice and work ability? Cochrane standards and QUOROM principals were used. For this systematic review the available literature was identified in a computerized search of the bibliographical databases Medline, Embase and Osh-rom. A total of 22 publications (24 studies) met the inclusion criteria. In the general practice population high prevalence rates of potentially work-related diseases were found for low back pain, neck pain and shoulder pain. Incidence rates of consulting a GP for a potentially work-related disease were high also. Musculoskeletal disorders were the main reasons for work-related consultations in general practice. Work-related diseases can affect work ability. Work-related diseases are common, given the high incidence and prevalence of potentially work-related diseases found in the general practice population and seen by the GP. This review underlines the important role of GPs in identifying and managing work-related diseases. GPs should consider the work factor and pay special attention to the effects of work on health, because patients often link their work with their illness.


Tuberculosis and hepatic steatosis are prevalent liver pathology findings among HIV-infected patients in South Africa.
Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.


Induction of markers of normal differentiation in human colon carcinoma cells by the v-rasH oncogene.
The molecular events that regulate differentiation of human colon mucosal cells are not known. Although a number of in vitro models to study this question exist, none have identified a gene product which could function as a mediator of cell differentiation. Although the Ki-ras gene is frequently mutated in human colon cancer, the Ha-ras protooncogene is maximally expressed in the most differentiated cells of intestinal mucosa. In order to study the effects of Ha-ras gene overexpression on the differentiation phenotype in human colon cancer cells, we have expressed the v-rasH oncogene in CaCO2 cells. This maneuver resulted in a marked induction of gene expression of multiple markers characteristic of intestinal brush border differentiation. These include a > or = 30-fold induction of sucrase, a 10-fold increase in intestinal alkaline phosphatase, a 20-fold induction of transforming growth factor alpha, and a 5-fold increase in transforming growth factor beta 1 steady-state mRNA levels. Finally, the CaCO2-ras cells undergo a > or = 95% reduction in DNA synthesis under serum-deficient conditions and cannot be restimulated after such treatment, suggesting terminal differentiation, whereas the same treatment has no effect on the proliferative capacity of the parent CaCO2 cell line. These studies with CaCO2 human colon cancer cells provide a model to study the role of v-rasH and related genes in colon epithelial differentiation.


Catalytic ozonation of bisphenol A in aqueous solution using Mn-Ce/HZSM-5 as catalyst.
Mixed manganese and cerium oxide supported on HZSM-5 were synthesized and used as heterogeneous catalysts for ozonation of bisphenol A (BPA) in aqueous solution. The prepared catalysts of Mn-Ce/HZSM-5 were characterized by X-ray diffraction, scanning electron microscopy and Fourier transform-infrared spectroscopy. The results indicated that Mn-Ce/HZSM-5 exhibits extraordinary catalytic activity for the degradation of BPA. Removal of 89.3% of BPA and 90.4% of total organic carbon (TOC) was achieved in 30 min, compared to non-catalytic ozonation, where only 50.5% BPA and 28.1% TOC removal were reached under the same conditions. Adsorption of BPA on HZSM-5 support and Mn-Ce/HZSM-5 catalysts was negligible. The strong inhibition of BPA removal by tert-butyl alcohol indicated that the attack of hydroxyl radicals was responsible for the improvement of catalytic ozonation. It was observed that at neutral pH, which is near the point of zero charge of the catalyst, the catalytic activity reached its maximum. Increasing the amount of Mn-Ce/HZSM-5 catalyst until it exceeded 3 g/L did not show a strong effect on BPA removal. The catalysts showed high stability and reusability.


Absence of true seroreversion of HIV-1 antibody in seroreactive individuals.
First, to determine whether there is evidence for loss of human immunodeficiency virus type 1 (HIV-1) antibody in seroreactive individuals. Second, if true seroreversion occurs, to determine its incidence relative to errors in the testing process. A retrospective cohort study reviewing the results of 5,446,161 HIV-1 antibody tests performed on 2,580,974 individuals (the US Army HIV Data System) from 1985 through 1992. For all patients with one or more seroreactive sample followed by one or more nonreactive sample, we examined available records and retested the samples. Serum samples had been obtained from active-duty and retired military personnel, their dependents, and applicants to the military. Of 4911 individuals reported to be seroreactive for HIV-1 by two independent samples, only six were potential seroreverters. Review of the six cases revealed that five actually were HIV-seroreactive patients who had samples from nonreactive individuals mistakenly attributed to them, while the sixth had a testing error proven by retesting the discrepant specimen. Errors in the testing process were identified (n = 23) or suspected (n = 3) in another 26 individuals who had not had independent confirmation of reactivity by a second sample. The cumulative error rate was 12.4 per 1 million patients tested. An additional group of 31 uninfected infants appeared to serorevert due to loss of antibody acquired from their HIV-1-infected mothers. Review of this database demonstrates no evidence for true seroreversion of HIV-1 antibody status. We conclude that if seroreversion occurs at all, it is exceedingly rare. In fact, most (if not all) cases of apparent seroreversion represent errors of attribution or testing.


Anatomic analysis of pedicle cortical and cancellous diameter as related to screw size.
The effective thoracic and lumbar pedicle diameter as related to screw size for that pedicle was studied in six fresh-frozen human cadaver spines. Measurements of the pedicle were obtained before screw insertion using axial and coronal reformatted computed tomographic (CT) images, as well as graduated sounding of the pedicle. After sequentially loading each pedicle with increasingly larger screws, measurements were taken of the outer cortical diameters. Plastic deformation of the pedicle preceded pedicle fracture or cutout when the screw thread diameter became larger than the endosteal diameter or within 80% of the outer cortical diameter as measured from the CT scan. Pedicle screws did not obtain cortical purchase within the pedicle.


Tetramerization and interdomain flexibility of the replication initiation controller YabA enables simultaneous binding to multiple partners.
YabA negatively regulates initiation of DNA replication in low-GC Gram-positive bacteria. The protein exerts its control through interactions with the initiator protein DnaA and the sliding clamp DnaN. Here, we combined X-ray crystallography, X-ray scattering (SAXS), modeling and biophysical approaches, with in vivo experimental data to gain insight into YabA function. The crystal structure of the N-terminal domain (NTD) of YabA solved at 2.7 Å resolution reveals an extended α-helix that contributes to an intermolecular four-helix bundle. Homology modeling and biochemical analysis indicates that the C-terminal domain (CTD) of YabA is a small Zn-binding domain. Multi-angle light scattering and SAXS demonstrate that YabA is a tetramer in which the CTDs are independent and connected to the N-terminal four-helix bundle via flexible linkers. While YabA can simultaneously interact with both DnaA and DnaN, we found that an isolated CTD can bind to either DnaA or DnaN, individually. Site-directed mutagenesis and yeast-two hybrid assays identified DnaA and DnaN binding sites on the YabA CTD that partially overlap and point to a mutually exclusive mode of interaction. Our study defines YabA as a novel structural hub and explains how the protein tetramer uses independent CTDs to bind multiple partners to orchestrate replication initiation in the bacterial cell.