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findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term.
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The Hudson River (HR) Estuary has a long history of pollution with a variety of contaminants including PCBs, and dioxins. In fact, 200 miles of the mainstem HR is designated a U.S. federal Superfund site, the largest in the nation, because of PCB contamination. The tidal HR hosts the southernmost spawning population of Atlantic tomcod, and studies revealed a correlation between exposure of juveniles to warm water temperature during summer to abundance of spawning adults of the same cohort in the following winter. Further, a battery of mechanistically linked biomarkers, ranging from the molecular to the population levels, were significantly impacted from contaminant exposures of the HR tomcod population. In response to xenobiotic insult, the HR tomcod population developed resistance to PCB sand TCDD toxicity resulting from a deletion in the aryl hydrocarbon receptor2 (AHR2) gene. Furthermore, RNA-Seq analysis of global gene expression demonstrated that effects of the AHR2 polymorphism were far more pervasive than anticipated. The most highly PCB-contaminated sediments in the upper HR were dredged between 2009 and 2015 with the objective of lowering PCB concentrations in fishes in the lower HR. Success of the remediation project has been controversial. These observations suggest that tomcod provides an informative model to evaluate the efficacy of HR PCB remediation efforts on downriver fish populations and possible interactive effects between contaminant exposure and a warming environment.
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Sturgeon populations worldwide are threatened with extirpation but little is known about their tendency to bioaccumulate contaminants and their sensitivities to environmental burdens of these contaminants. Shortnose sturgeon and Atlantic sturgeon, two species that are federally endangered in the USA, co-occur in the Hudson River (HR) where high sediment levels of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-p-furans (PCDFs) occur. Previous controlled laboratory studies showed that young life-stages of both species are sensitive to toxicities at low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and PCB126 exposure. The objective here was to measure congener-specific hepatic levels of PCBs and PCDD/Fs in HR specimens in order to determine if in situ bioaccumulation of these compounds is sufficiently high to have caused the early life-stage toxicities previously observed. Estimates of hepatic burdens of PCBs and PCDD/Fs were obtained from a small number of specimens of each species collected between 2014 and 2016 and specimens of shortnose sturgeon collected over 30 years earlier and archived in a museum collection. Several significant patterns emerged. Hepatic levels of legacy PCBs and PCDDs were low in specimens of both species but typically higher in shortnose than Atlantic sturgeon, a pattern consistent with their habitat use in the HR. Hepatic burdens in shortnose sturgeon tended to be higher in archived specimens than in more recently collected ones despite expected reduction in archived specimens due to preservation methods. Several inadvertent PCBs congeners were detected at high levels, including PCB11, but their toxicity to natural populations remains unknown. Levels of select PCDFs congeners, 2,3,7,8-TCDF and 2,3,4,7,8 PeCDF, were elevated in some shortnose sturgeon individuals from the HR. Using Relative Potency (ReP) factors derived from white sturgeon, the observed levels of some hepatic PCDFs in HR shortnose sturgeon may have been sufficiently high to impair recruitment of young life-stages in this ecosystem.
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Bifenilos Policlorados , Dibenzodioxinas Policloradas , Poluentes Químicos da Água , Animais , Dibenzofuranos , Dibenzofuranos Policlorados , Ecossistema , Peixes , Humanos , New York , Bifenilos Policlorados/análise , Bifenilos Policlorados/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/toxicidade , Rios , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Significant advances in pharmacological treatments for mental illness and addiction will require abandoning old monoaminergic theories of psychiatric disorders and traditionally narrow approaches to how we conduct treatment research. Reframing our efforts with a view on integrative treatments that target core neural network function and plasticity may provide new approaches for lifting patients out of chronic psychiatric symptom sets and addiction. For example, we discuss new treatments that target brain glutamate systems at key transition points within longitudinal courses of care that integrate several treatment modalities. A reconsideration of what our novel and already available medications are intended to achieve and how and when we deliver them for patients with complex illness trajectories could be the key to unlocking new advances in general and addiction psychiatry.
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Anger is a common behaviour exhibited by road users when one's goals are perceived to have been blocked by another. Recent research has demonstrated that, generally, cyclists tend to deal with anger in constructive ways. However, when anger does manifest, it can result in behaviours that increase their crash risk. Amongst motor vehicle drivers, mindfulness levels have been associated with less anger and appear to mediate anger and associated aggression. The current study sought to understand whether mindfulness has similar associations with anger and aggression in a sample of cyclists. A total of 583 cyclists (males = 68 %) completed an online questionnaire that sought information on their levels of mindfulness, current mindfulness practices and tendencies for anger and aggression while cycling. The relationships between these were then examined using structural equation modelling. The results showed that cyclists with higher mindfulness levels tended to report less anger across a range of situations (e.g., interactions with pedestrians, cyclists, motor vehicle drivers and police). Both direct and indirect (through anger) relationships were found between mindfulness and aggression, again showing that more mindful cyclists tended to engage in less frequent aggression. These findings align with recent research investigating this relationship amongst motor vehicle drivers and suggest that mindfulness may be a promising strategy to reduce or avoid anger and aggression in cyclists.
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Ciclismo/psicologia , Atenção Plena , Fúria no Trânsito/psicologia , Acidentes de Trânsito/prevenção & controle , Adulto , Ciclismo/estatística & dados numéricos , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Pedestres/estatística & dados numéricos , Fúria no Trânsito/estatística & dados numéricos , Autorrelato , Inquéritos e QuestionáriosRESUMO
Multiple addictions frequently occur in patients with mental illness. However, basic research on the brain-based linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35-60). Starting in adulthood (PD 63), rats acquired lever pressing for concurrent oral alcohol (10% with 2% sucrose) and iv nicotine (0.015 mg/kg/injection) across 15 sessions. Subsequently, 10 operant extinction sessions and 3 reinstatement sessions examined drug seeking upon withholding of nicotine, then both nicotine and alcohol, then reintroduction. Adolescent alcohol consumption did not differ between NVHLs and controls. However, in adulthood, NVHLs showed increased lever pressing at alcohol and nicotine levers that progressed more strongly at the nicotine lever, even as most pressing by both groups was at the alcohol lever. In extinction, both groups showed expected declines in effort as drugs were withheld, but NVHLs persisted with greater pressing at both alcohol and nicotine levers. In reinstatement, alcohol reaccess increased pressing, with NVHLs showing greater nicotine lever activity overall. Developmental temporal-limbic abnormalities that produce mental illness can thus generate adult polydrug addiction vulnerability as a mechanism independent from putative cross-sensitization effects between addictive drugs. Further preclinical modeling of third-order (and higher) addiction-mental illness comorbidities may advance our understanding and treatment of these complex, yet common brain illnesses.
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Alcoolismo/complicações , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Esquizofrenia/complicações , Tabagismo/complicações , Alcoolismo/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Etanol/administração & dosagem , Masculino , Nicotina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Esquizofrenia/fisiopatologia , Autoadministração , Tabagismo/fisiopatologiaRESUMO
In 1939, British psychiatrist Lionel Penrose described an inverse relationship between mental health treatment infrastructure and criminal incarcerations. This relationship, later termed the 'Penrose Effect', has proven remarkably predictive of modern trends which have manifested as reciprocal components, referred to as 'deinstitutionalization' and 'mass incarceration'. In this review, we consider how a third dynamic-the criminalization of addiction via the 'War on Drugs', although unanticipated by Penrose, has likely amplified the Penrose Effect over the last 30 years, with devastating social, economic, and healthcare consequences. We discuss how synergy been the Penrose Effect and the War on Drugs has been mediated by, and reflects, a fundamental neurobiological connection between the brain diseases of mental illness and addiction. This neuroscience of dual diagnosis, also not anticipated by Penrose, is still not being adequately translated into improving clinical training, practice, or research, to treat patients across the mental illness-addictions comorbidity spectrum. This failure in translation, and the ongoing fragmentation and collapse of behavioral healthcare, has worsened the epidemic of untreated mental illness and addictions, while driving unsustainable government investment into mass incarceration and high-cost medical care that profits too exclusively on injuries and multi-organ diseases resulting from untreated addictions. Reversing the fragmentation and decline of behavioral healthcare with decisive action to co-integrate mental health and addiction training, care, and research-may be key to ending criminalization of mental illness and addiction, and refocusing the healthcare system on keeping the population healthy at the lowest possible cost.
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Prestação Integrada de Cuidados de Saúde , Transtornos Mentais/terapia , Serviços de Saúde Mental/organização & administração , Prisões/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/terapia , Diagnóstico Duplo (Psiquiatria) , Humanos , Transtornos Mentais/epidemiologia , Serviços de Saúde Mental/economia , Prisões/economia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Sturgeon species are imperiled world-wide by a variety of anthropogenic stressors including chemical contaminants. Atlantic sturgeon, Acipenser oxyrinchus, and shortnose sturgeon, Acipenser brevirostrum, are largely sympatric acipenserids whose young life-stages are often exposed to high levels of benthic-borne PCBs and PCDD/Fs in large estuaries along the Atlantic Coast of North America. In previous laboratory studies, we demonstrated that both sturgeon species are sensitive to early life-stage toxicities from exposure to environmentally relevant concentrations of coplanar PCBs and TCDD. The sensitivity of young life-stages of fishes to these contaminants varies among species by three orders of magnitude and often is due to variation in the structure and function of the aryl hydrocarbon receptor (AHR) pathway. Unlike mammals, fishes have two forms of AHR (AHR1 and AHR2) with AHR2 usually being more highly expressed across tissues and functional in mediating toxicities. Based on previous studies in white sturgeon, A. transmontanus, we hypothesized that sturgeon taxa are unusually sensitive to these contaminants because of higher levels of expression and functional activity of AHR1 than in other fish taxa. To address this possibility, we characterized AHR1 in both Atlantic Coast sturgeon species, evaluated its' in vivo expression in young life-stages and in multiple tissues of shortnose sturgeon, and tested its ability to drive reporter gene expression in AHR-deficient cells treated with graded doses of PCB126 and TCDD. Similar to white sturgeon and lake sturgeon, AHR1 amino acid sequences in Atlantic sturgeon and shortnose sturgeon were more similar to mammalian AHRs and avian AHR1s than to AHR1 in other fishes, suggesting their greater functionality in sturgeon species than in other fishes. Exposure to graded doses of coplanar PCBs and TCDD usually failed to significantly induce AHR1 expression in young life-stages or most tissues of shortnose sturgeon. However, in reporter gene assays, AHR1 drove higher levels of gene expression than AHR2 alone, but their binary combination failed to drive higher levels of expression than either AHR alone. In total, our results suggest that AHR1 may be more functional in sturgeon species than in other fishes, but probably does not explain their heightened sensitivity to these contaminants.
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Peixes , Regulação da Expressão Gênica/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Peixes/genética , Peixes/metabolismo , Perfilação da Expressão Gênica , América do Norte , Bifenilos Policlorados/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Psychological and pharmacological treatments have been shown to reduce rates of transition to psychosis in Ultra High Risk (UHR) young people. However, social functioning deficits have been unresponsive to current treatments. AIMS: The study aims were to: i) describe the theoretical basis and therapeutic targets of a novel intervention targeting social functioning in UHR young people; and ii) examine its acceptability, safety and preliminary effect on social functioning. METHODS: An international, multidisciplinary team developed a new intervention (MOMENTUM) to improve social functioning in UHR young people. MOMENTUM blends two novel approaches to social recovery: strengths and mindfulness-based intervention embedded within a social media environment, and application of the self-determination theory of motivation. The acceptability and safety of MOMENTUM were tested through a 2-month pilot study with 14 UHR participants. RESULTS: System usage was high, with over 70% of users being actively engaged over the trial. All participants reported a positive experience using MOMENTUM, considered it safe and would recommend it to others. 93% reported it to be helpful. There were large, reliable improvements in social functioning (dâ¯=â¯1.83, pâ¯<â¯0.001) and subjective wellbeing (dâ¯=â¯0.75, pâ¯=â¯0.03) at follow-up. There were significant increases in the mechanisms targeted by the intervention including strengths usage (dâ¯=â¯0.70, pâ¯=â¯0.03), mindfulness skills (dâ¯=â¯0.66, pâ¯=â¯0.04) and components of social support. Social functioning improvement was significantly correlated with indicators of system usage. CONCLUSION: MOMENTUM is engaging and safe. MOMENTUM appeared to engage the hypothesized mechanisms and showed promise as a new avenue to improve social functioning in UHR young people.
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Internet , Atenção Plena/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Transtornos Psicóticos/reabilitação , Autoeficácia , Rede Social , Apoio Social , Terapia Socioambiental/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Risco , Adulto JovemRESUMO
Atlantic sturgeon and shortnose sturgeon co-occur in many estuaries along the Atlantic Coast of North America. Both species are protected under the U.S. Endangered Species Act and internationally on the IUCN Red list and by CITES. Early life-stages of both sturgeons may be exposed to persistent aromatic hydrocarbon contaminants such as PCBs and PCDD/Fs which are at high levels in the sediments of impacted spawning rivers. Our objective was to compare the PCBs and TCDD sensitivities of both species with those of other fishes and to determine if environmental concentrations of these contaminants approach those that induce toxicity to their young life-stages under controlled laboratory conditions. Because our previous studies suggested that young life-stages of North American sturgeons are among the more sensitive of fishes to coplanar PCB and TCDD-induced toxicities, we were interested in identifying the molecular bases of this vulnerability. It is known that activation of the aryl hydrocarbon receptor 2 (AHR2) in fishes mediates most toxicities to these contaminants and transcriptional activation of xenobiotic metabolizing enzymes such as cytochrome P4501A (CYP1A). Previous studies demonstrated that structural and functional variations in AHRs are the bases for differing sensitivities of several vertebrate taxa to aromatic hydrocarbons. Therefore, in this study we characterized AHR2 and its expression in both sturgeons as an initial step in understanding the mechanistic bases of their sensitivities to these contaminants. We also used CYP1A expression as an endpoint to develop Toxicity Equivalency Factors (TEFs) for these sturgeons. We found that critical amino acid residues in the ligand binding domain of AHR2 in both sturgeons were identical to those of the aromatic hydrocarbon-sensitive white sturgeon, and differed from the less sensitive lake sturgeon. AHR2 expression was induced by TCDD (up to 6-fold) and by three of four tested coplanar PCB congeners (3-5-fold) in Atlantic sturgeon, but less so in shortnose sturgeon. We found that expression of AHR2 and CYP1A mRNA significantly covaried after exposure to TCDD and PCB77, PCB81, PCB126, but not PCB169 in both sturgeons. We also determined TEFs for the four coplanar PCBs in shortnose sturgeon based on comparison of CYP1A mRNA expression across all doses. Surprisingly, the TEFs for all four coplanar PCBs in shortnose sturgeon were much higher (6.4-162 times) than previously adopted for fishes by the WHO.
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Citocromo P-450 CYP1A1/metabolismo , Peixes/metabolismo , Bifenilos Policlorados/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Sequência de Aminoácidos , Animais , Arocloros/toxicidade , Citocromo P-450 CYP1A1/genética , Peixes/genética , Peixes/crescimento & desenvolvimento , Regulação da Expressão Gênica/efeitos dos fármacos , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Hidrocarboneto Arílico/química , Receptores de Hidrocarboneto Arílico/genética , Poluentes Químicos da Água/toxicidadeRESUMO
Abnormalities in brain white matter (WM) structure have been reported in youths having a family history of substance use disorders (SUDs). It was hypothesized that these abnormalities constitute features of the liability for SUDs transmitted across generations. The association between severity of intergenerational risk for SUD, measured by the Transmissible Liability Index (TLI), and white matter microstructure was examined. Diffusion tensor imaging (DTI) measured WM microstructure in forty-four drug-naïve 10-14 year-olds (N = 19 with parental SUD). Metrics of WM microstructure (i.e., fractional anisotropy, radial diffusivity, mean diffusivity and axial diffusivity) were quantified across the whole brain and in four tracts of interest: anterior corona radiata, superior and inferior longitudinal fasciculi and superior fronto-occipital fasciculi. The TLI was completed by the youths, their parents and, when available, their teachers. The relationship between WM structure and TLI score across the entire group was evaluated using linear multiple regression and between group comparisons were also examined. Fractional anisotropy and radial diffusivity in multiple tracts across the brain were significantly associated with TLI scores. Confirming and extending prior research, the findings indicate that global atypicality in WM tracts was linearly related to liability for eventual SUD development in drug naïve youths.
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Comportamento Aditivo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Predisposição Genética para Doença , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Comportamento Aditivo/genética , Comportamento Aditivo/patologia , Encéfalo/anormalidades , Encéfalo/patologia , Criança , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Vias Neurais/anormalidades , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Pais , Análise de Regressão , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/patologia , Substância Branca/anormalidades , Substância Branca/patologiaRESUMO
ABSTRACT The Doctor of Medicine (DM) in Paediatrics Programme began in 1972 in Jamaica and was the first four-year clinical residency programme to be offered at The University of the West Indies (UWI). The DM Paediatrics programme trains residents for four-years and equips them after completion to practice as consultant paediatricians. Over the forty-five years of offering this programme, 237 students have been enrolled and 159 students have successfully completed the course. Over ninety per cent of the graduates are Caribbean nationals. Graduates from the DM Paediatrics programme at Mona are currently serving in Jamaica and other Caribbean countries, the United States of America (USA), Canada, Australia and the United Kingdom. Approximately, 24% have pursued subspecialty training and 60% work in a hospital-based setting while 30% work in private practice and 27% in academia and research. There are some of these that combine hospital ward work with academia and research. The DM (Paediatrics) Programme at the UWI, Mona, has achieved its mandate of providing paediatricians for Jamaica and the Caribbean and is committed to continue to train paediatricians to meet existing paediatric healthcare needs in Jamaica and the Caribbean.
RESUMEN El Programa de Doctor en Medicina (DM) en Pediatría comenzó en 1972 en Jamaica y fue el primer programa de residencia clínica de cuatro años que se ofreció en la Universidad de West Indies (UWI). El programa DM de Pediatría entrena a los residentes durante cuatro años y los faculta después de su terminación para practicar como pediatras consultores. En los 45 años de este programa, 237 estudiantes han sido matriculados y 159 estudiantes han completado con éxito el curso. Más del 90 por ciento de los graduados son nacionales del Caribe. Los egresados del programa DM de Pediatría de Mona prestan actualmente sus servicios en Jamaica y otros países del Caribe, los Estados Unidos de América (EE. UU.), Canadá, Australia y el Reino Unido. Aproximadamente, el 24% han continuado su formación en subespecialidades; el 60% trabaja en el medio hospitalario, mientras que el 30% trabaja en la práctica privada; y el 27% en la academia y la investigación. Algunos de ellos combinan el trabajo en las salas de hospitales con la academia y la investigación. El programa DM (Pediatría) de UWI, Mona, ha logrado su mandato de proveer pediatras para Jamaica y el Caribe, y se compromete a seguir capacitando a pediatras para que satisfagan las necesidades de salud pediátrica existentes en Jamaica y el Caribe.
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Humanos , Masculino , Feminino , Pediatria/educação , Educação Médica Continuada/estatística & dados numéricos , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Internato e Residência/estatística & dados numéricos , Estudantes , Pediatras/educação , JamaicaRESUMO
Interpersonal attachment and drug addiction share many attributes across their behavioral and neurobiological domains. Understanding the overlapping brain circuitry of attachment formation and addiction illuminates a deeper understanding of the pathogenesis of trauma-related mental illnesses and comorbid substance use disorders, and the extent to which ending an addiction is complicated by being a sort of mourning process. Attention to the process of addiction recovery-as a form of grieving-in which Kubler-Ross's stages of grief and Prochaska's stages of change are ultimately describing complementary viewpoints on a general process of neural network and attachment remodeling, could lead to more effective and integrative psychotherapy and medication strategies.
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Pesar , Recuperação da Saúde Mental/tendências , Neurociências , Apego ao Objeto , Transtornos Relacionados ao Uso de Substâncias/terapia , Adaptação Psicológica , Animais , Comportamento Aditivo , Encéfalo/fisiologia , Humanos , PsicoterapiaRESUMO
RATIONAL: Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability. OBJECTIVES: In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes. METHODS: Rats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1; n = 80) or nicotine self-administration (experiment 2; n = 12). RESULTS: In experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio ("FLETR"; p < 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R 2 = 0.14, p < 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R 2 = 0.47, p < 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement. CONCLUSIONS: These findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC-hippocampal-striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.
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Acetilcisteína/farmacologia , Comportamento Aditivo/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/farmacologia , Comportamento de Procura de Droga/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Animais , Animais Recém-Nascidos , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Masculino , Transtornos da Memória/patologia , Memória de Curto Prazo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND AND OBJECTIVES: Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. METHODS: Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders. RESULTS: There were no group differences post-injection in treatment days, injections delivered, or treatment service encounters. UDS and PDMP measures of opioid exposures were greater in opioid compared to alcohol-only patients. Post-first injection, UDS's positive for opioids declined (p < .05) along with PDMP measures of opioid prescriptions (p < .001), doses (p < .01), types (p < .001), numbers of dispensing prescribers (p < .001) and pharmacies (p < .001). Opioid patients without alcohol disorders showed the best outcomes with 50% to 80% reductions in PDMP-measures of opioids, down to levels of alcohol-only patients. CONCLUSIONS: This study shows PDMP utility for measuring opioid addiction treatment outcomes, supporting the routine use of PDMPs in clinical and research settings. SCIENTIFIC SIGNIFICANCE: These findings demonstrate that opioid addiction in patients with complex addictions and mental illnesses comorbidities can show effective treatment responses as measured by PDMP tracking of decreases in opioid prescriptions to those patients. (Am J Addict 2016;25:557-564).
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Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Programas de Monitoramento de Prescrição de Medicamentos , Adulto , Transtornos Relacionados ao Uso de Álcool/complicações , Analgésicos Opioides/urina , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Injeções Intravenosas , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Detecção do Abuso de Substâncias , Resultado do TratamentoRESUMO
Chikungunya virus (CHIKV) entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica. METHODS: This study reviewed the public health effects of the illness in Jamaica by reviewing available data sources and the clinical features in 210 children and adolescents meeting the case definition at two hospitals, Bustamante Hospital for Children and University Hospital of the West Indies between August 23 and October 31, 2014 by chart review. Descriptive analyses and comparisons between groups using the Mann-Whitney U test were performed with SPSS version 22. RESULTS: The majority of households were affected by the illness which caused widespread absenteeism from school and work, loss of productivity and economic losses estimated at 60 billion dollars. The health sector was impacted by increased numbers seen in clinics and emergency departments, increased need for bed space and pharmaceuticals. Ninety-nine per cent of the children were febrile with a median maximal temperature of 102.4 F. Ninety-three per cent had household contacts of 020 persons. In addition to fever, maculopapular rash and joint pains, infants six months and younger presented with irritability and groaning (p = 0.00) and those between six months and six years presented with febrile seizures (p = 0.00). Neurologic involvement was noted in 24%. Apart from anaemia, few had other laboratory derangements. Few had severe organ dysfunction and there were no deaths. CONCLUSION: The Chikungunya Fever epidemic had significant public health and economic impact in Jamaica. In children, there were characteristic presentations in neonates and young infants and in children six months to six years. Neurologic involvement was common but other organ dysfunction was rare. These findings underscore the need to prevent further epidemics and the quest for a vaccine.(AU)
Antecedentes: El virus de Chikungunya (CHIKV) entró en el Caribe por primera vez en 2013, y Jamaica experimentó su primera epidemia de fiebre de Chikungunya en 2014. Nos propusimos como objetivo describir sus efectos en la salud pública y describir sus características clínicas en niños y adolescentes en Jamaica. Métodos: Este estudio examinó los efectos de la enfermedad en la salud pública en Jamaica. El examen se realizó mediante la revisión de fuentes de datos disponibles y las características clínicas en 210 niños y adolescentes que cumplían con la definición del caso en dos hospitales Hospital Pediátrico Bustamante y el Hospital Universitario de West Indies entre el 23 de agosto y 31 de octubre de 201, según las historias clínicas. Se realizaron análisis descriptivos y comparaciones entre los grupos usando la prueba U de Mann-Whitney y la versión 22 de SPSS Resultados: La mayoría de los hogares fueron afectados por la enfermedad, que causó un ausentismo generalizado en escuelas y trabajos, pérdida de productividad, y pérdidas económicas estimadas en 60 billones de dólares. El sector de la salud fue afectado por un aumento del número de personas atendidas en clínicas y departamentos de urgencias, y una mayor necesidad de camas en los hospitales y productos farmacéuticos. Noventa y nueve por ciento de los niños presentaron un estado febril con una temperatura mediana máxima de 102.4 F. Un noventa y tres por ciento tuvo contactos domésticos de personas de 020. Además de fiebre, erupciones maculopapulares y dolores en las articulaciones, los niños de seis meses o menos edad, presentaron irritabilidad y quejidos (p = 0.00), y aquellos entre seis meses y seis años de edad presentaron convulsiones febriles (p = 0.00). Se observó compromiso neurológico en el 24%. Aparte de anemia, algunos tenían otros trastornos de laboratorio. Otros presentaban una disfunción orgánica severa y no hubo muertes. Conclusión: La epidemia de fiebre de Chikungunya tuvo un impacto significativo tanto en la salud pública como en la economía de Jamaica. Los niños presentaron manifestaciones características, observadas tanto en recién nacidos y bebés pequeños como en niños de seis meses a seis años. El compromiso neurológico fue común, pero cualquiera otra disfunción orgánica fue rara. Estos hallazgos subrayan la necesidad de hacer más por evitar las epidemias y buscar la solución de una vacuna.(AU)
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Arbovírus , Vírus Chikungunya , Saúde Pública , Jamaica/epidemiologiaRESUMO
Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) has proven to be a powerful technique revealing complexity and diversity of natural DOM molecules, but its application to DOM analysis in grazing-impacted agricultural systems remains scarce. In the present study, we presented a case study of using ESI-FTICR-MS in analyzing DOM from four headwater streams draining forest- or pasture-dominated watersheds in Virginia, USA. In all samples, most formulas were CHO compounds (71.8-87.9%), with other molecular series (CHOS, CHON, CHONS, and CHOP (N, S)) accounting for only minor fractions. All samples were dominated by molecules falling in the lignin-like region (H/C = 0.7-1.5, O/C = 0.1-0.67), suggesting the predominance of allochthonous, terrestrial plant-derived DOM. Relative to the two pasture streams, DOM formulas in the two forest streams were more similar, based on Jaccard similarity coefficients and nonmetric multidimensional scaling calculated from Bray-Curtis distance. Formulas from the pasture streams were characterized by lower proportions of aromatic formulas and lower unsaturation, suggesting that the allochthonous versus autochthonous contributions of organic matter to streams were modified by pasture land use. The number of condensed aromatic structures (CAS) was higher for the forest streams, which is possibly due to the controlled burning in the forest-dominated watersheds and suggests that black carbon was mobilized from soils to streams. During 15-day biodegradation experiments, DOM from the two pasture streams was altered to a greater extent than DOM from the forest streams, with formulas with H/C and O/C ranges similar to protein (H/C = 1.5-2.2, O/C = 0.3-0.67), lipid (H/C = 1.5-2.0, O/C = 0-0.3), and unsaturated hydrocarbon (H/C = 0.7-1.5, O/C = 0-0.1) being the most bioreactive groups. Aromatic compound formulas including CAS were preferentially removed during combined light+bacterial incubations, supporting the contention that black carbon is labile to light alterations. Collectively, our data demonstrate that headwater DOM composition contains integrative information on watershed sources and processes, and the application of ESI-FTICR-MS technique offers additional insights into compound composition and reactivity unrevealed by fluorescence and stable carbon isotopic measurements.
Assuntos
Florestas , Análise de Fourier , Compostos Orgânicos/química , Rios/química , Espectrometria de Massas por Ionização por Electrospray , Monitoramento Ambiental , LuzRESUMO
Tremendous growth in opioid prescribing over two decades in the USA has correlated with proportional increases in diversion, addiction, and overdose deaths. Pseudoaddiction, a concept coined in 1989, has frequently been cited to indicate that under-treatment of pain, rather than addiction, is the more pressing and authentic clinical problem in opioid-seeking patients. This investigative review searched Medline articles containing the term "pseudoaddiction" to determine its footprint in the literature with a focus on how it has been characterized and empirically validated. By 2014, pseudoaddiction was discussed in 224 articles. Only 18 of these articles contributed to or questioned pseudoaddiction from an anecdotal or theoretical standpoint, and none empirically tested or confirmed its existence. Twelve of these articles, including all four that acknowledged pharmaceutical funding, were proponents of pseudoaddiction. These papers described pseudoaddiction as an iatrogenic disease resulting from withholding opioids for pain that can be diagnosed, prevented, and treated with more aggressive opioid treatment. In contrast, six articles, none with pharmaceutical support, questioned pseudoaddiction as a clinical construct. Empirical evidence supporting pseudoaddiction as a diagnosis distinct from addiction has not emerged. Nevertheless, the term has been accepted and proliferated in the literature as a justification for opioid therapy for non-terminal pain in patients who may appear to be addicted but should not, from the perspective of pseudoaddiction, be diagnosed with addiction. Future studies should examine whether acceptance of pseudoaddiction has complicated accurate pain assessment and treatment, and whether it has contributed to or reflected medical-cultural shifts that produced the iatrogenic opioid addiction epidemic.
RESUMO
This study developed and applied an approach to calculate the proportion of fish gut content composed of mucus secreted by the oropharyngeal cavity and gut. The amount of nitrogen in the contents of the foregut (oesophagus and gizzard) and the epibranchial organs of suspension-feeding American gizzard shad Dorosoma cepedianum was significantly higher than the nitrogen in the homogeneous food source. Using data collected from suspension-feeding experiments and the nitrogen content of D. cepedianum mucus, a series of equations illustrated that mucus constituted c. 10% of D. cepedianum foregut content and 12% of epibranchial organ content by dry mass. Future quantification of fish feeding selectivity and absorption efficiency can use this approach to take into account the contribution of fish mucus to the nutrients in the gut contents. This study supports the conclusion that suspension-feeding D. cepedianum in a heterogeneous environment selectively ingest nutrient-rich particles, even when gut nutrient content is adjusted to take into account the contribution of mucus.
Assuntos
Ração Animal , Peixes , Muco/química , Nitrogênio/química , Animais , Esôfago/metabolismo , Comportamento Alimentar , Moela não Aviária/metabolismoRESUMO
RATIONAL: Nicotine use in schizophrenia has traditionally been explained as "self-medication" of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. OBJECTIVES: We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. METHODS: Nicotine transdermal patch (5 mg/kg/day vs. placebo × 10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4ß2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. RESULTS: NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food-reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of ß2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p < 0.05) but not ventral striatum (<5% changes, p > .40), whereas nicotine history elevated nAChRs across both regions (>30%, p < 0.001) without interacting with NVHLs. Adolescent vs. adult nicotine exposure did not alter nAChRs differentially. CONCLUSIONS: Although replicating nicotine-induced upregulation of nAChRs in human smokers and demonstrating NVHL validity in terms of schizophrenia-associated nAChR density patterns, these findings do not support hypotheses explaining increased nicotine use in schizophrenia as reflecting illness-specific effects of nicotine to therapeutically alter cognition or nAChR densities.