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Background: Patient navigation increases linkage to hepatitis C virus (HCV) care following release from prison; however, little is known about the services patient navigators should provide to maximize linkage to care. We aimed to identify perceived barriers and facilitators to linkage to HCV care post-release, and to determine patient navigator services and characteristics best suited to address barriers to linkage to care among people released from prison., Methods: Ten semi-structured interviews were conducted with adult (age ≥18 years) men living with chronic HCV, released from the largest Quebec provincial prison, and linked to HCV care by a patient navigator. Interviews were guided by the Socio-Ecological Model (SEM) and aimed to explore the multi-level barriers and facilitators to linkage to HCV care post-release. Interviews were audio-recorded, transcribed, and analyzed using a deductive, thematic approach., Results: The median age of participants was 54 years. Barriers to linkage to HCV care included competing priorities post-release (e.g., substance use, mental health issues, unstable housing), stigma (related to HCV, injection drug use, and incarceration), and lack of transportation. Facilitators included social support, established relationships with existing healthcare providers, prior cure with direct-acting antivirals, and HCV-related health literacy and knowledge. Perceived essential patient navigator services to enhance linkage included pre-release discharge appointments, housing assistance, and facilitated transportation to HCV appointments. Ensuring a consistent, non-judgemental, and empathetic patient navigator were considered important characteristics; lived experiences of incarceration and/or HCV were not felt to be essential for a patient navigator., Conclusions: Interventions that seek to improve linkage to HCV care for people following release from prison should address many levels (individual, interpersonal, and policy) of the SEM. While people experience several competing priorities post-release, having an empathetic and consistent patient navigator, regardless of their lived experiences of HCV and/or incarceration, may improve linkage to HCV care post-release., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AM, LR, DOP, CD, SC, LdB, AP, ML, and AH report no competing interests. NK reports grants for investigator-initiated studies from ViiV Healthcare, Abbvie, and Gilead, advisory fees from Gilead Sciences, ViiV Healthcare, Merck, and Abbvie, and speaker fees from Gilead Sciences, Abbvie, and Merck, all outside this work. GS has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead, and has received unrestricted research funding from Theratecnologies Inc. MBK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, Merck and Gilead, and consulting fees from ViiV Healthcare, AbbVie and Gilead, all outside the submitted work. BL has received consultancy fees and/or honoraria and research funds from Gilead, ViiV Healthcare, and Merck. JC has received research funding from ViiV Healthcare, Merck, and Gielead, consulting fees from ViiV Healthcare and Gilead, and payment for lectures from Gilead, all outside this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Analysis of circulating tumor DNA (ctDNA) is increasingly used for clinical decision-making in oncology. However, ctDNA could represent ≤ 0.1 % of cell-free DNA in early-stage tumors and its detection requires high-sensitive techniques such as digital PCR (dPCR)., Methods: In 46 samples from patients with early-stage breast cancer, we compared two leading dPCR assays for ctDNA analysis: QX200 droplet digital PCR (ddPCR) system from Bio-Rad which is the gold-standard in the field, and Absolute Q plate-based digital PCR (pdPCR) system from Thermo Fisher Scientific which has not been reported before. We analyzed 5 mL of baseline plasma samples prior to any treatment., Results: Both systems displayed a comparable sensitivity with no significant differences observed in mutant allele frequency. In fact, ddPCR and pdPCR possessed a concordance > 90 % in ctDNA positivity. Nevertheless, ddPCR exhibited higher variability and a longer workflow. Finally, we explored the association between ctDNA levels and clinicopathological features. Significantly higher ctDNA levels were present in patients with a Ki67 score > 20 % or with estrogen receptor-negative or triple-negative breast cancer subtypes., Conclusion: Both ddPCR and pdPCR may constitute sensitive and reliable tools for ctDNA analysis with an adequate agreement in early-stage breast cancer patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Apples are the third most produced fruit in the world, but their production is often pesticide-intensive. Our objective was to identify options for pesticide reduction using farmer records from 2549 commercial apple fields in Austria during five years between 2010 and 2016. Using generalized additive mixed modeling, we examined how pesticide use was related to farm management, apple varieties, and meteorological parameters, and how it affected yields and toxicity to honeybees. Apple fields received 29.5 ± 8.6 (mean ± SD) pesticide applications per season at a rate of 56.7 ± 22.7 kg ha -1 , which included a total of 228 pesticide products with 80 active ingredients. Over the years, fungicides accounted for 71 % of the pesticide amounts applied, insecticides for 15 %, and herbicides for 8 %. The most frequently used fungicides were sulfur (52 %), followed by captan (16 %) and dithianon (11 %). Of insecticides, paraffin oil (75 %) and chlorpyrifos/chlorpyrifos-methyl (6 % combined) were most frequently used. Among herbicides, glyphosate (54 %), CPA (20 %) and pendimethalin (12 %) were most often used. Pesticide use increased with increasing frequency of tillage and fertilization, increasing field size, increasing spring temperatures, and drier summer conditions. Pesticide use decreased with increasing number of summer days with maximum temperatures >30 °C and number of warm, humid days. Apple yields were significantly positively related to the number of heat days, warm humid nights, and pesticide treatment frequency, but were not affected by frequency of fertilization and tillage. Honeybee toxicity was not related to insecticide use. Pesticide use and yield were significantly related to apple varieties. Our analysis shows that pesticide use in the apple farms studied can be reduced by less fertilization and tillage, partly because yields were >50 % higher than the European average. However, weather extremes related to climate change, such as drier summers, could challenge plans to reduce pesticide use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Organophosphates are insecticides that inhibit the enzymatic activity of acetylcholinesterase (AChE). Because of this, AChE is considered a physiological marker of organophosphate exposure in agricultural settings. However, limited research exists on the associations between urinary organophosphate metabolites and AChE activity in children., Methods: This study included 526 participants from 2 exams (April and July-October 2016) of ages 12-17 years living in agricultural communities in Ecuador. AChE activity was measured at both examinations, and organophosphate metabolites, including para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), and malathion dicarboxylic acid (MDA) were measured in urine collected in July-October. We used generalized estimating equation generalized linear model (GEEGLM), adjusting for hemoglobin, creatinine, and other demographic and anthropometric covariates, to estimate associations of urinary metabolite concentrations with AChE activity (July-October) and AChE% change between April and July-October., Results: The mean (SD) of AChE and AChE% change (April vs July-October) were 3.67 U/mL (0.54) and -2.5% (15.4%), respectively. AChE activity was inversely associated with PNP concentration, whereas AChE% change was inversely associated with PNP and MDA. There was evidence of a threshold: difference was only significant above the 80th percentile of PNP concentration (AChE difference per SD increase of metabolite = -0.12 U/mL [95%CI: 0.20, -0.04]). Likewise, associations with AChE% change were significant only above the 80th percentile of TCPy (AChE % change per SD increase of metabolite = -1.38% [95%CI: 2.43%, -0.32%]) and PNP -2.47% [95%CI: 4.45%, -0.50%]). PNP concentration at ≥80th percentile was associated with elevated ORs for low AChE activity of 2.9 (95% CI: 1.5, 5.7) and for AChE inhibition of ≤ -10% of 3.7 (95% CI: 1.4, 9.8)., Conclusions: Urinary organophosphate metabolites, including PNP, TCPy and MDA, particularly at concentrations above the 80th percentile, were associated with lower AChE activity among adolescents. These findings bring attention to the value of using multiple constructs of pesticide exposure in epidemiologic studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Limited evidence exists regarding transient neurobehavioral alterations associated with episodic pesticide exposures or agricultural pesticide spray periods. We previously observed that children examined soon after a pesticide spray period (the Mother's Day flower harvest [MDH]) had lower neurobehavioral performance than children examined later. The present study builds on our previous work by incorporating longitudinal analyses from childhood through adolescence., Methods: We examined participants in agricultural communities in Ecuador (ESPINA study) during three periods: July-August 2008 (N = 313, 4-9-year-olds); April 2016 (N = 330, 11-17-year-olds); July-October 2016 (N = 535, 11-17-year-olds). Participants were examined primarily during a period of low floricultural production. Neurobehavior was assessed using the NEPSY-II (domains: Attention/Inhibitory Control, Language, Memory/Learning, Visuospatial Processing, and Social Perception). Linear regression and generalized linear mixed models were used to examine cross-sectional and longitudinal associations between examination date (days) after the MDH and neurobehavioral outcomes, adjusting for demographic, anthropometric, and socio-economic variables., Results: Participants were examined between 63 and 171 days after the MDH. Mean neurobehavioral domain scores ranged from 1.0 to 17.0 (SD range  = 2.1-3.1) in 2008 and 1.0 to 15.5 (SD range  = 2.0-2.3) in 2016. In cross-sectional analyses (2016 only; N = 523), we found significant or borderline positive associations between time after the MDH and Attention/Inhibitory Control (difference/10 days [β] = 0.22 points [95% CI = 0.03, 0.41]) and Language (β = 0.16 points [95% CI = -0.03, 0.34]). We also observed positive, longitudinal associations (2008-2016) with Attention/Inhibitory Control (β = 0.19 points [95% CI = 0.04, 0.34]) through 112 days after the harvest and Visuospatial Processing (β = 3.56, β-quadratic = -0.19 [95% CI: -0.29, -0.09]) through 92 days., Conclusions: Children examined sooner after the harvest had lower neurobehavioral performance compared to children examined later, suggesting that peak pesticide spray seasons may transiently affect neurobehavior followed by recovery during low pesticide-use periods. Reduction of pesticide exposure potential for children during peak pesticide-use periods is advised., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The study of non-typhoid Salmonella in broiler integrations has been limited by the resolution of typing techniques. Although serotyping of Salmonella isolates is used as a traditional approach, it is not of enough resolution to clearly understand the dynamics of this pathogen within poultry companies. The aim of this research was to investigate the epidemiology and population dynamics of Salmonella serotypes in 2 poultry integrations using a whole genome sequencing approach. Two hundred and forty-three Salmonella isolates recovered from the broiler production chain of 2 integrated poultry companies were whole genome sequenced and analyzed with dedicated databases and bioinformatic software. The analyses of sequences revealed that S. Infantis was the most frequent serotype (82.3%). Most isolates showed a potential for resistance against medically important antibiotics and disinfectants. Furthermore, 97.5% of isolates harbored the pESI-like mega plasmid, that plays an important role in the global dissemination of AMR. SNP tree analysis showed that there were clones that are niche-specific while other ones were distributed throughout the broiler production chains. In this study, we demonstrated the potential of whole genome sequencing analysis for a comprehensive understanding of Salmonella distribution in integrated poultry companies. Data obtained with these techniques allow determination of the presence of genetic factors that play an important role in the environmental fitness and pathogenicity of Salmonella., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Direct acting antivirals (DAAs) have increased cure rates for hepatitis C virus (HCV) infection; however, there are several obstacles to the uptake of DAAs in populations where substance use contributes to HCV risk. This synthesis aimed to identify the patient and provider perceived barriers and facilitators to DAA treatment initiation in key patient subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and Indigenous people., Methods: We systematically searched seven databases and conducted a gray literature search for studies that qualitatively explored patient and provider perceived barriers and facilitators to DAA treatment in our populations of interest. Selected studies were published after 2013 when second generation DAAs became available. The titles, abstracts, and subsequently full texts were screened by two independent reviewers and critically appraised. Barriers and facilitators to DAA treatment uptake were then extracted and thematically synthesized., Results: 2144 titles and abstracts were identified and screened; 29 full texts were subsequently reviewed. Twelve qualitative studies were finally included. Among providers, perceived barriers to DAA treatment uptake included lack of resources and lack of provider knowledge on HCV while facilitators to treatment provision included simplicity of DAA regimens and professional identity as a doctor to advocate for patients. Among patients, perceived barriers to treatment uptake included current drug use, concerns about side effects of DAAs, stigma, gaps in community care, competing social responsibilities and mental health issues while facilitators included having a trustworthy provider and access to multidisciplinary HCV care., Conclusion: Despite simplicity of DAAs, many structural barriers to optimal HCV care continue to be experienced by patients and providers. In highlighting nuanced patient and provider perceived barriers and facilitators, this review underscores the need to involve participatory methods in the design and evaluation of interventions to best improve access to care., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. A. Amoako, K. Engler and D. Ortiz-Paredes have no declaration of interests. M.B. Klein has had research support from ViiV Healthcare, Abbvie, Merck and Gilead and received consulting fees from ViiV and AbbVie, and Gilead. She is supported by a Tier I Canada Research Chair. B. Lebouchéis the Canadian Institutes for Health Research, Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials for HIV Care and is also supported by a career award LE 250 from the Quebec’s Ministry of Health for researchers in Family Medicine., (Copyright © 2021. Published by Elsevier B.V.)

Neural stimulation is a powerful tool to study brain physiology and an effective treatment for many neurological disorders. Conventional interfaces use electrodes implanted in the brain. As these are often invasive and have limited spatial targeting, they carry a potential risk of side-effects. Smaller neural devices may overcome these obstacles, and as such, the field of nanoscale and remotely powered neural stimulation devices is growing. This review will report on current untethered, injectable nanomaterial technologies intended for neural stimulation, with a focus on material-tissue interface engineering. We will review nanomaterials capable of wireless neural stimulation, and discuss their stimulation mechanisms. Taking cues from more established nanomaterial fields (e.g., cancer theranostics, drug delivery), we will then discuss methods to modify material interfaces with passive and bioactive coatings. We will discuss methods of delivery to a desired brain region, particularly in the context of how delivery and localization are affected by surface modification. We will also consider each of these aspects of nanoscale neurostimulators with a focus on their prospects for translation to clinical use., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: To date, reported SARS-CoV-2 reinfection cases are mainly from strains belonging to different clades. As the pandemic advances, a few lineages have become dominant in certain areas leading to reinfections by similar strains. Here, we report a reinfection case within the same clade of the initial infection in a symptomatic 28-year-old-male in Quito-Ecuador., Methods: Infection was detected by reverse transcription-polymerase chain reaction, and immune response evaluated by antibody testing. Whole-genome sequencing was performed and phylogenetic analysis conducted to determine relatedness., Results: Both the infection and the reinfection strains were assigned as Nextstrain 20B, Pangolin lineage B.1.1 and GISAID clade O. Our analysis indicated 4-6 fold more nucleotide changes than are expected for reactivation or persistence compared with the natural rate of SARS-CoV-2 mutation (∼2-3 nucleotide changes per month), thus supporting reinfection. Furthermore, approximately 3 months after the second infection, COVID-19 antibodies were not detectable in the patient, suggesting potential vulnerability to a third infection., Conclusions: Our results showed evidence of SARS-CoV-2 reinfection within the same clade in Ecuador, indicating that previous exposure to SARS-CoV-2 does not guarantee immunity in all cases., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Off-target drift of pesticides from farms increases the risk of pesticide exposure of people living nearby. Cholinesterase inhibitors (i.e. organophosphates and carbamates) are frequently used in agriculture and inhibit acetylcholinesterase (AChE) activity. Greenhouse agriculture is an important production method, but it is unknown how far pesticide drift from greenhouses can extend and expose people living nearby., Methods: This study included 1156 observations from 3 exams (2008, Apr, 2016 and Jul-Oct 2016) of 623 children aged 4-to-17 years living in agricultural communities in Ecuador. AChE, a physiological marker of cholinesterase inhibitor exposure, was measured in blood. Geographic positioning of greenhouses and homes were obtained using GPS receivers and satellite imagery. Distances between homes and the nearest greenhouse edge, and areas of greenhouse crops within various buffer zones around homes were calculated. Repeated-measures regression adjusted for hemoglobin and other covariates estimated change in AChE relative to distance from greenhouses., Results: The pooled mean (SD) of AChE activity was 3.58 U/mL (0.60). The median (25th-75th %tile) residential distance to crops was 334 m (123, 648) and crop area within 500 m of homes (non-zero values only) was 18,482 m 2 (7115, 61,841). Residential proximity to greenhouse crops was associated with lower AChE activity among children living within 275 m of crops (AChE difference per 100 m of proximity [95% CI] = -0.10 U/mL [-0.20, -0.006]). Lower AChE activity was associated with greater crop area within 500 m of homes (AChE difference per 1000 m2 [95% CI] = -0.026 U/mL [-0.040, -0.012]) and especially within 150 m (-0.037 U/mL [-0.065, -0.007])., Conclusions: Residential proximity to floricultural greenhouses, especially within 275 m, was associated with lower AChE activity among children, reflecting greater cholinesterase inhibitor exposure from pesticide drift. Analyses of residential proximity and crop areas near homes yielded complementary findings. Mitigation of off-target drift of pesticides from crops onto nearby homes is recommended., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The performance of constructed wetlands (CW) can be enhanced through the use of microbial electrochemical technologies like METland systems. Given its novelty, uncertainties exist regarding processes responsible for the pollutant removal and microbial activity within the systems. Genetic characterization of microbial communities of METlands is desirable, but it is a time and resource consuming. An alternative, is the functional analysis based on community-level physiological profile (CLPP), which allows to evaluate the diversity of microbial communities based on the carbon consumption patterns and derived indexes (average well color development - AWCD -, richness, and diversity). This study aimed to characterize the microbial community function of laboratory-scale METlands using the CLPP method. It encompassed the analysis of planted and non-planted set-ups of two carbon-based electroconductive materials (Coke-A and Coke-LSN) colonized with electroactive biofilms, and compared to Sand-filled columns. Variations in the microbial metabolic activity were found to depend on the characteristics of the material rather than to the presence of plants. Coke-A systems showed lower values of AWCD, richness, and diversity than Sand and Coke-LSN systems. This suggests that Coke-A systems provided more favorable conditions for the development of relatively homogeneous microbial biofilms. Additionally, typical parameters of water quality were measured and correlations between utilization of carbon sources and removal of pollutants were established. The results provide useful insight into the spatial dynamics of the microbial activity of METland systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A highly sensitive method was developed to measure putrescine by micellar electrokinetic chromatography with laser induced fluorescence detection with excellent linearity in the 1 nM to 3 μM range. The technique was tested on a drop of blood from Parkinson's disease patients obtained by finger prick. The results showed a statistically significant increase of putrescine in the erythrocytes compared to controls and a non-significant increase in plasma. This high level of putrescine does not constitute by itself proof that putrescine and polyamines are directly related to Parkinson's disease. However, the present results and several others addressed in the discussion suggest that these compounds might be causally involved in the pathophysiology of Parkinson's disease. In addition, the analytical method reported here may help to find new biomarkers for many diseases including Parkinson's disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Chile is a post-transitional country evolving towards a stationary population pyramid, which may be associated with increasing preterm birth (PTB) rates. This study aimed to compare maternal sociodemographic characteristics between the start of the post-transition phase (1994) and an established stage (2013) and to evaluate associations between these characteristics and PTB., Study Design: An observational analytic design was conducted using national birth records (n = 4,956,311)., Methods: Variables analysed in the 20 birth cohorts from 1994 to 2013 were: length of gestation (preterm <37 weeks) subdivided by gestational age (extreme, moderate/severe and late); maternal age (≤19, 20-35 and >35 years); education level (<8, 8-12 and >12 years of education); employment; marital status; area of residence; and type of birth (singleton, twins, and triplets or higher order). The prevalence of PTB was expressed as a percentage, and associations between PTB and predictor variables were analysed using logistic regression models., Results: Education level, age >35 years, maternal employment, unmarried status, twin delivery and urban residency rates increased between 1994 and 2013. According to the adjusted models, age >35 years and delivery of more than two foetuses were risk factors for all PTB subtypes. Maternal employment was a risk factor for moderate/severe, late and total PTB, and a low level of education was a risk factor for late and total PTB. On the other hand, age ≤19 years was protective against all PTB subtypes., Conclusions: All maternal characteristics changed between 1994 and 2013. Furthermore, the prevalence of PTB increased for all predictor variables studied over this period., (Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

It has been suggested that vascular stasis during cardio-circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out-of-hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98-100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. As well, we observed correlations between thromboelastomeric lysis parameters and maximum hepatic transaminase levels measured in potential donors and renal artery flows measured during ex situ hypothermic oxygenated machine perfusion, indicating that further studies on the utility of thromboelastometry to evaluate organ injury and perhaps even viability in unexpected DCDD may be warranted., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Mycobacterium timonense is a non-tuberculous mycobacteria (NTM) described in southern France in 2009, and to our knowledge, not reported again as a human pathogen in indexed literature. The aim of this work was to characterize the first clinical isolate of M. timonense in Ecuador. Time of growth, biochemical tests, thin layer growth test, PCR-RFLP analysis of the hsp65 gene and MALDI-TOF spectra analysis were not able to identify the species. The species identification was achieved through sequencing of rrs, hsp65 and rpoB genes. The results highlight the necessity to set up a sequencing method to identify emerging NTM in Ecuadorian clinical facilities., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Agmatine is a putative neurotransmitter in the brain. Current analytical techniques do not allow the detection of agmatine in extracellular fluid, making it difficult to study its physiological role. However, a new method for in vivo monitoring agmatine in the brain was developed. Capillary zone electrophoresis and laser induced fluorescence detection (CZE-LIFD) was used to measure nanomolar concentrations of agmatine in submicroliter sample volumes. This analytical technique proved to detect 0.49 attomole of agmatine improving the sensitivity of previous analytical techniques. On the other hand, the hippocampus is a brain region well known for having a population of agmatine containing neurons. Therefore, intracerebral microdialysis was performed in the hippocampus and agmatine was extracted from the extracellular environment. Detectable amounts of agmatine were found in dialysates from probes located in the hippocampus but not from the probes located in the lateral ventricle. Furthermore, extracellular agmatine was calcium and impulse dependent and depolarization of hippocampal neurons increased extracellular agmatine concentration. The methods reported here are sensitive enough to study the physiological role of brain agmatine in freely moving animals., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Stress is causally associated with anxiety. Although the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons have been implicated in stress response. p75(NTR) is a panneurotrophin receptor expressed almost exclusively in basal forebrain cholinergic neurons in adult brain. This study investigated whether and how p75(NTR), via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress-related behaviors., Methods: We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis, and neuronal activity mapping to assess the role of p75(NTR) in mood and stress-related behaviors and its underlying cellular and molecular mechanisms., Results: We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice but not in mice lacking p75(NTR). The p75(NTR) mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75(NTR) perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75(NTR) deletion., Conclusions: Our results suggest that loss of p75(NTR) leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Abnormal hedonic behavior is a key feature of many psychiatric disorders. Several paradigms measure reward-seeking behavior in rodents, but each has limitations. We describe a novel approach for monitoring reward-seeking behavior in rodents: sniffing of estrus female urine by male mice, along with number of ultrasonic vocalizations (USVs) emitted during the test., Methods: The female urine sniffing test (FUST) was designed to monitor reward-seeking activity in rodents together with tests of helplessness and sweet solution preference. USVs and dopamine release from the nucleus accumbens (NAc) were recorded. Sniffing activity was measured in 1) manipulation-naive C57BL/6J and 129S1/SVImJ mice and Wistar-Kyoto rats; 2) stressed mice; 3) two groups of mice that underwent the learned helplessness paradigm-one untreated, and one treated with the SSRI citalopram; and 4) GluR6 knockout mice, known to display lithium-responsive, mania-related behaviors., Results: Males from all three strains spent significantly longer sniffing female urine than sniffing water. Males emitted USVs and showed significantly elevated NAc dopamine levels while sniffing urine. Foot-shock stress significantly reduced female urine sniffing time. Compared with mice that did not undergo the LH paradigm, LH males spent less time sniffing female urine, and citalopram treatment alleviated this reduction. Compared with their wildtype littermates, GluR6KO males sniffed female urine longer and showed enhanced saccharin preference., Conclusions: In rodents, sniffing female urine is a preferred activity accompanied by biological changes previously linked to reward-seeking activities. The FUST is sensitive to behavioral and genetic manipulation and to relevant drug treatment., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: During the last years the number of patients on waiting list for kidney transplantation has been stable. Living donor kidney transplantation is nowadays a chance to increase the pool of donors. However, there are a group of patients with ABO incompatibility, making impossible the transplant until now. The aim of the present study is to describe the experience of Hospital Clinic Barcelona on ABO incompatible living transplantation., Methods: A retrospective- descriptive study was made based on 11 living donor kidney recipients with ABO incompatibility in Hospital Clinic of Barcelona from October'06 to January'09. Selective blood group, antibody removal with specific immunoadsortion, immunoglobulin and anti- CD 20 antibody were made until the immunoglobulin (IgG) and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive protocol was adjusted to particular recipient characteristics. Isoaglutinine titters were set before, during and post desensitization treatment and two weeks after transplant. Immunological, medical and surgical evaluation was the standard in living donor kidney transplant program., Results: Medium age of donors and recipients were 47.8 +/- 12.4 and 44.4 +/- 14.1 years, respectively. 90% of donors were females and 73% of recipients males. Follow-up time was 10.2 +/- 10.2 months. Siblings and spouses were the most frequent relation (n=4, 36.4%, respectively). Chronic glomerulonephritis, adult polycystic kidney disease and Alport syndrome, the most frequent cause of end-stage renal disease. All the patients acquire appropriate isoaglutinine titters pre transplant (< 1/8), requiring 5.54 +/- 2.6 immunoadsorption sessions pretransplant and 2.82 posttransplant. One patient didn t need any immunoadsorption session (incompatibility blood group B) and another patient plasma exchange instead of immunoadsorption for being hypersensitized with positive flow cytometry crossmatch. Posttransplant isoaglutinine titters remained low. Two patients had cellular acute rejection episode (type IA and IB of Banff classification) with good response to corticosteroid treatment. Patient and graft survival were 91% at first year and remain stable during the follow-up. A graft lost by death of patient in relation to haemorrhagic shock developed within the first 72 hours after transplantation. Renal graft function at first year was excellent with serum creatinine of 1.3 +/- 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73 m2 and proteinuria of 244.9 mg/U-24h., Conclusion: ABO incompatible living donor kidney transplantation represent an effective and safe alternative in certain patients on waiting list for renal transplant, obtaining excellent results in patient and graft survival, with good renal graft function.

A major stumbling block in acquiring a new skill can be integrating it with old but related knowledge. Learning multiplication is a case in point, because it involves integrating new relations with previously acquired arithmetic knowledge (in particular, addition). Two studies explored developmental changes in the relations between single-digit addition and multiplication. In the first study, third-graders, fifth-graders, and adults performed simple addition or multiplication in mixed- and blocked-operations formats. Substantial interfering effects from related knowledge were found at all age levels, but were more pronounced for younger subjects. Thus in the early stages of learning multiplication, one consequence of learning a new operation is interference in performance of an earlier, related, but less recently studied skill. Consideration of error patterns supported the view that the problem of integrating operations is a prominent one even in the early stages of mastering multiplication. Patterns of errors were generally consistent across all age groups, and all groups were much more likely to give a correct multiplication response to an addition problem than the reverse. A second, longitudinal study confirmed this finding, showing evidence for impaired performance of addition over time within individual children (second-, third-, and fourth-graders) tested on simple addition and multiplication over a 5-month period. Analysis of reaction times for addition indicated that second-graders in advanced math classes and third-graders in regular math classes tended to slow down over the year in responses to addition problems. Fourth-graders, on the other hand, tended to increase their speed of addition over the course of the year. Multiplication showed a different pattern during this period, with no evidence for slowing among children who were able to perform this task. Disruption of previously learned knowledge in the course of acquiring new skills provides evidence that new knowledge and old knowledge are being integrated. This kind of non-monotonic development may provide an empirical method for determining the functional limits of a domain of knowledge.