Electrokinetic Management of Biosolids for the Inactivation of Helminth Ova

The presumed risk to public health has led to a growing interest in the production of exceptional quality biosolids intended to contain undetectable levels of three classes of pathogens: bacteria, enteric viruses, and helminth eggs (parasitic intestinal worms). This study assessed the performance of an enhanced electrokinetic technology which permits the simultaneous dewatering, heavy metal removal and inactivation of the swine helminth, Ascaris suum, from wastewater sludge in one operational unit for the production of exceptional quality biosolids. The process is based on the electrokinetic (EK) phenomena, initiated by the introduction of direct electric current through the biosolids, preceded by a brief period of ohmic heating. A series of bench-scale tests were performed on combined primary and secondary sewage sludges obtained from the wastewater treatment plant in Auteuil, QC. Two additional tests were repeated at a pilot scale with success. The results demonstrated that the enhanced EK treatment is capable of delivering a product virtually free of viable Ascaris suum ova introduced to the conditioned sludge with a brief exposure at a temperature of 55°C. In addition, dewatering levels up to 23 % total solids (TS) and mean removal levels of over 54 %, 30 %, and 24 % for heavy metals such as Zn, Cd, and Pb, respectively, within a period of 3 days were reported. Consequently, the sanitized biosolids generated during the enhanced EK treatment process can be transformed into a high quality soil amendment that could be safely applied to agricultural lands

Identification of Cryptic MHC I–restricted Epitopes Encoded by HIV-1 Alternative Reading Frames

Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti–HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses

Suppression of the intrinsic apoptosis pathway by sinaptic activity

Synaptic activity promotes resistance to diverse apoptotic insults, the mechanism behind which is incompletely understood. We show here that a coordinated downregulation of core components of the intrinsic apoptosis pathway by neuronal activity forms a key part of the underlying mechanism. Activity-dependent protection against apoptotic insults is associated with inhibition of cytochrome c release in most but not all neurons, indicative of anti-apoptotic signaling both upstream and downstream of this step. We find that enhanced firing activity suppresses expression of the proapoptotic BH3-only member gene Puma in a NMDA receptor-dependent, p53-independent manner. Puma expression is sufficient to induce cytochrome c loss and neuronal apoptosis. Puma deficiency protects neurons against apoptosis and also occludes the protective effect of synaptic activity, while blockade of physiological NMDA receptor activity in the developing mouse brain induces neuronal apoptosis that is preceded by upregulation of Puma. However, enhanced activity can also confer resistance to Puma-induced apoptosis, acting downstream of cytochrome c release. This mechanism is mediated by transcriptional suppression of apoptosome components Apaf-1 and procaspase-9, and limiting caspase-9 activity, since overexpression of procaspase-9 accelerates the rate of apoptosis in active neurons back to control levels. Synaptic activity does not exert further significant anti-apoptotic effects downstream of caspase-9 activation, since an inducible form of caspase-9 overrides the protective effect of synaptic activity, despite activity-induced transcriptional suppression of caspase-3. Thus, suppression of apoptotic gene expression may synergize with other activity-dependent events such as enhancement of antioxidant defenses to promote neuronal survival

Mood Induction in Depressive Patients: A Comparative Multidimensional Approach

Anhedonia, reduced positive affect and enhanced negative affect are integral characteristics of major depressive disorder (MDD). Emotion dysregulation, e.g. in terms of different emotion processing deficits, has consistently been reported. The aim of the present study was to investigate mood changes in depressive patients using a multidimensional approach for the measurement of emotional reactivity to mood induction procedures. Experimentally, mood states can be altered using various mood induction procedures. The present study aimed at validating two different positive mood induction procedures in patients with MDD and investigating which procedure is more effective and applicable in detecting dysfunctions in MDD. The first procedure relied on the presentation of happy vs. neutral faces, while the second used funny vs. neutral cartoons. Emotional reactivity was assessed in 16 depressed and 16 healthy subjects using self-report measures, measurements of electrodermal activity and standardized analyses of facial responses. Positive mood induction was successful in both procedures according to subjective ratings in patients and controls. In the cartoon condition, however, a discrepancy between reduced facial activity and concurrently enhanced autonomous reactivity was found in patients. Relying on a multidimensional assessment technique, a more comprehensive estimate of dysfunctions in emotional reactivity in MDD was available than by self-report measures alone and this was unsheathed especially by the mood induction procedure relying on cartoons. The divergent facial and autonomic responses in the presence of unaffected subjective reactivity suggest an underlying deficit in the patients' ability to express the felt arousal to funny cartoons. Our results encourage the application of both procedures in functional imaging studies for investigating the neural substrates of emotion dysregulation in MDD patients. Mood induction via cartoons appears to be superior to mood induction via faces and autobiographical material in uncovering specific emotional dysfunctions in MDD

Brain Circuitries Involved in Semantic Interference by Demands of Emotional and Non-Emotional Distractors

BACKGROUND: Previous studies have indicated that the processes leading to the resolution of emotional and non-emotional interference conflicts are unrelated, involving separate networks. It is also known that conflict resolution itself suggests a considerable overlap of the networks. Our study is an attempt to examine how these findings may be related. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging (fMRI) to study neural responses of 24 healthy subjects to emotional and non-emotional conflict paradigms involving the presentation of congruent and incongruent word-face pairs based on semantic incompatibility between targets and distractors. In the emotional task, the behavioral interference conflict was greater (compared to the non-emotional task) and was paralleled by involvement of the extrastriate visual and posterodorsal medial frontal cortices. In both tasks, we also observed a common network including the dorsal anterior cingulate, the supplemental motor area, the anterior insula and the inferior prefrontal cortex, indicating that these brain structures are markers of experienced conflict. However, the emotional task involved conflict-triggered networks to a considerably higher degree. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that responses to emotional and non-emotional distractors involve the same systems, which are capable of flexible adjustments based on conflict demands. The function of systems related to conflict resolution is likely to be adjusted on the basis of an evaluation process that primarily involves the extrastriate visual cortex, with target playing a significant role

Neurobiological Divergence of the Positive and Negative Schizophrenia Subtypes Identified on a New Factor Structure of Psychopathology Using Non-negative Factorization:An International Machine Learning Study

ObjectiveDisentangling psychopathological heterogeneity in schizophrenia is challenging and previous results remain inconclusive. We employed advanced machine-learning to identify a stable and generalizable factorization of the “Positive and Negative Syndrome Scale (PANSS)”, and used it to identify psychopathological subtypes as well as their neurobiological differentiations.MethodsPANSS data from the Pharmacotherapy Monitoring and Outcome Survey cohort (1545 patients, 586 followed up after 1.35±0.70 years) were used for learning the factor-structure by an orthonormal projective non-negative factorization. An international sample, pooled from nine medical centers across Europe, USA, and Asia (490 patients), was used for validation. Patients were clustered into psychopathological subtypes based on the identified factor-structure, and the neurobiological divergence between the subtypes was assessed by classification analysis on functional MRI connectivity patterns.ResultsA four-factor structure representing negative, positive, affective, and cognitive symptoms was identified as the most stable and generalizable representation of psychopathology. It showed higher internal consistency than the original PANSS subscales and previously proposed factor-models. Based on this representation, the positive-negative dichotomy was confirmed as the (only) robust psychopathological subtypes, and these subtypes were longitudinally stable in about 80% of the repeatedly assessed patients. Finally, the individual subtype could be predicted with good accuracy from functional connectivity profiles of the ventro-medial frontal cortex, temporoparietal junction, and precuneus.ConclusionsMachine-learning applied to multi-site data with cross-validation yielded a factorization generalizable across populations and medical systems. Together with subtyping and the demonstrated ability to predict subtype membership from neuroimaging data, this work further disentangles the heterogeneity in schizophrenia

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

33% capacity improvement of a direct-modulation direct-detection OFDM link using adaptive Volterra equalization

Capacity increase larger than 33% of an optimized Direct-modulation Direct-detection OFDM link is experimentally demonstrated. This was achieved by optimizing Volterra filter design

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which mediate the general pathological aspects of septicemia. Here we explored an alternative strategy by using genetically engineered nonreplicating, nonlytic phage to combat an experimental Pseudomonas aeruginosa infection. An export protein gene of the P. aeruginosa filamentous phage Pf3 was replaced with a restriction endonuclease gene. This rendered the Pf3 variant (Pf3R) nonreplicative and concomitantly prevented the release of the therapeutic agent from the target cell. The Pf3R phage efficiently killed a wild-type host in vitro, while endotoxin release was kept to a minimum. Treatment of P. aeruginosa infections of mice with Pf3R or with a replicating lytic phage resulted in comparable survival rates upon challenge with a minimal lethal dose of 3. However, the survival rate after phage therapy with Pf3R was significantly higher than that with the lytic phage upon challenge with a minimal lethal dose of 5. This higher survival rate correlated with a reduced inflammatory response elicited by Pf3R treatment relative to that with the lytic phage. Therefore, this study suggests that the increased survival rate of Pf3R-treated mice could result from reduced endotoxin release. Thus, the use of a nonreplicating modified phage for the delivery of genes encoding proteins toxic to bacterial pathogens may open up a new avenue in antimicrobial therapy