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BACKGROUND: The number of persons using opioids has increased worldwide in the last decade, particularly the use of opioid analgesics in North America and Africa. In Germany, the prevalence of heroin addiction has remained relatively stable. METHOD: Narrative review of the literature. RESULTS: Opioid-assisted maintenance treatment (OMT) with the established substances methadone, levomethadone, slow-release morphine and buprenorphine is recommended as the first-line treatment for heroin dependence. The OMT reduces the use of heroin, mortality and individual suffering and improves the quality of life and physical health. A diamorphine and heroine-assisted treatment is an option for people who do not benefit from conventional OMT. An alternative to the use of diamorphine could be treatment with hydromorphone hydrochloride. The regulations on carrying out maintenance treatment in the Controlled Substances Prescription Act and the guidelines of the Federal Medical Association in Germany have been loosened based on the experiences of the COVID-19 pandemic, for example with respect to take-home prescriptions. There is an ongoing intensive discussion on how to deal with the decreasing number of outpatient clinics offering OMT. CONCLUSION: The first-line treatment for opioid addiction is opioid-assisted substitution treatment, including diamorphine and heroin-assisted treatment. Long-acting depot medications and implants still play a subordinate role.
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Addiction medicine is currently facing new challenges, such as drug epidemics and open drug scenes. It is responding to these challenges with a range of innovations: 1. The commercialization of opioid-assisted treatment (OAT) is a major step forward. 2. In Geneva, a community outreach project involving mental health peer practitioners targets the emerging crack scene, demonstrating its effectiveness in directing this marginalized population towards care. 3. In Switzerland, two projects in French-speaking Switzerland are testing hybrid models of cannabis regulation. Evaluation of these projects will guide the best approach to cannabis regulation.
L'addictologie est actuellement confrontée à des nouveaux défis, tels que des épidémies de consommation et des scènes de drogues ouvertes. Elle répond à ces défis par différentes innovations. 1. La commercialisation du traitement assisté par opioïdes (TAO) en dépôt est une avancée majeure. 2. À Genève, un projet communautaire de maraudes, impliquant des pairs praticiens en santé mentale, cible la scène de consommation de crack émergente, montrant son efficacité pour orienter cette population marginalisée vers les soins. 3. En Suisse, deux projets romands testent des modèles hybrides de régulation du cannabis. L'évaluation de ces projets guidera la meilleure approche pour la régulation du cannabis.
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Medicina de las Adicciones , Conducta Adictiva , Cannabis , Epidemias , Alucinógenos , Humanos , Analgésicos OpioidesRESUMEN
Correct cellular localization is essential for the function of many eukaryotic proteins and hence cell physiology. Here, we present a synthetic genetic device that allows the control of nuclear and cytosolic localization based on controlled alternative splicing in human cells. The device is based on the fact that an alternative 3' splice site is located within a TetR aptamer that in turn is positioned between the branch point and the canonical splice site. The novel splice site is only recognized when the TetR repressor is bound. Addition of doxycycline prevents TetR aptamer binding and leads to recognition of the canonical 3' splice site. It is thus possible to produce two independent splice isoforms. Since the terminal loop of the aptamer may be replaced with any sequence of choice, one of the two isoforms may be extended by the respective sequence of choice depending on the presence of doxycycline. In a proof-of-concept study, we fused a nuclear localization sequence to a cytosolic target protein, thus directing the protein into the nucleus. However, the system is not limited to the control of nuclear localization. In principle, any target sequence can be integrated into the aptamer, allowing not only the production of a variety of different isoforms on demand, but also to study the function of mislocalized proteins. Moreover, it also provides a valuable tool for investigating the mechanism of alternative splicing in human cells.
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Empalme Alternativo , Aptámeros de Nucleótidos/metabolismo , Señales de Localización Nuclear/metabolismo , Sitios de Empalme de ARN , Proteínas Represoras/metabolismo , Transporte Activo de Núcleo Celular/efectos de los fármacos , Empalme Alternativo/efectos de los fármacos , Aptámeros de Nucleótidos/síntesis química , Aptámeros de Nucleótidos/genética , Emparejamiento Base , Secuencia de Bases , Sitios de Unión , Núcleo Celular/química , Núcleo Celular/metabolismo , Citosol/química , Citosol/metabolismo , Doxiciclina/farmacología , Exones , Células HeLa , Humanos , Intrones , Modelos Moleculares , Señales de Localización Nuclear/química , Señales de Localización Nuclear/genética , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Proteínas Represoras/química , Proteínas Represoras/genéticaRESUMEN
BACKGROUND: Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM. METHODS: This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated. RESULTS: Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported. CONCLUSIONS: After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.
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Dependencia de Heroína , Trastornos Relacionados con Opioides , Humanos , Heroína , Analgésicos Opioides/uso terapéutico , Estudios de Factibilidad , Suiza , Dependencia de Heroína/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
BACKGROUND: Heroin-assisted treatment has proven effective in reducing criminal offenses in opioid dependent individuals. Few studies attempted to explain the observed crime reduction and the reasons why these patients keep offending and getting incarcerated have to date not been explored. METHODS: Patients with a history of incarcerations during the time of participating in heroin-assisted treatment (n = 22) were invited to a semi-structured, narrative interview. Findings were evaluated with Mayring's qualitative content analysis framework. Additionally, the Montreal Cognitive Assessment test and the multiple-choice vocabulary intelligence test used to assess cognitive impairment and premorbid intelligence levels. RESULTS: Three main categories emerged in patients' narratives on their incarcerations: cocaine use, impaired functioning, and financial constraints. Lifetime prevalence of cocaine use disorder was 95.5% and their cocaine use often led to patients getting incarcerated. Impaired functioning mainly constituted the inability to receive and open mail. Financial constraints led to incarcerations in lieu of payment in 16 participants (72.7%). Categories overlapped notably and often occurred in close temporal proximity. A fourth category on the likelihood of getting incarcerated again in the future was inhomogeneous and ranged from the strong conviction to complete rejection of the scenario. Average premorbid intelligence levels were found, whereas the cognitive assessment suggested severe cognitive impairment in our sample. CONCLUSION: Participants mainly reported to have committed minor offenses and not being able to pay for resulting fines. The resulting prison sentences are an unconvincing practice from a medical and economic perspective alike. Public expenditure and the interruptions of the continuum of care could be reduced by legislatively protecting these marginalised patients.
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Cocaína , Prisioneros , Trastornos Relacionados con Sustancias , Crimen , Heroína , Humanos , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
INTRODUCTION: Opioid agonist treatment (OAT) is the first-line treatment for opioid dependence. Currently available OAT options comprise oral (methadone and morphine) and sublingual (buprenorphine) routes of administration. In Switzerland and some other countries, severely opioid-dependent individuals with insufficient response to oral or sublingual OAT are offered heroin-assisted treatment (HAT), which involves the provision of injected or oral medical heroin (diacetylmorphine [DAM]). However, many patients on treatment with injectable DAM (i-HAT) suffer from injection-related problems such as deteriorated vein status, ulcerations, endocarditis, and abscesses. Other patients who do not respond to oral OAT do not inject but snort opioids, and are not eligible for i-HAT. For this population, there is no other short-acting OAT with rapid onset of action available unless they switch to injecting, which is associated with higher risks. Nasal DAM (n-HAT) could be an alternative treatment option suitable for both populations of patients. METHODS: We present a case series of 3 patients on i-HAT who successfully switched to n-HAT. RESULTS/CONCLUSIONS: This is the first description of the clinical use of the nasal route of administration for HAT. n-HAT may constitute an important risk-reduced rapid-onset alternative to i-HAT. In particular, it may be suited for patients with injection-related complications, or noninjecting opioid-dependent patients failing to respond to oral OAT.
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Buprenorfina , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Buprenorfina/uso terapéutico , Heroína/uso terapéutico , Humanos , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
BACKGROUND: Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset ("rush") but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts. CASE PRESENTATION: A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff. CONCLUSIONS: Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.
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Dependencia de Heroína , Heroína , Administración Intranasal , Adulto , Analgésicos Opioides/uso terapéutico , Heroína/uso terapéutico , Dependencia de Heroína/tratamiento farmacológico , Humanos , Inyecciones Intravenosas , Masculino , Morfina/uso terapéuticoRESUMEN
Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.
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Sobredosis de Droga , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Niño , Sobredosis de Droga/prevención & control , Humanos , Tamizaje Masivo/métodos , Salud Mental , Trastornos Relacionados con Sustancias/prevención & control , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The tetracycline-binding RNA aptamer (TC-aptamer) is a synthetic riboswitch that binds the antibiotic tetracycline (TC) with exceptionally high affinity. Although a crystal structure exists of the TC-bound state, little is known about the conformational dynamics and changes upon ligand binding. In this study, pulsed electron paramagnetic resonance techniques for measuring distances (PELDOR) in combination with rigid nitroxide spin labels (Çm spin label) were used to investigate the conformational flexibility of the TC-aptamer in the presence and absence of TC at different Mg2+ concentrations. TC was found to be the essential factor for stabilizing the tertiary structure at intermediate Mg2+ concentrations. At higher Mg2+ concentrations, Mg2+ alone is sufficient to stabilize the tertiary structure. In addition, the orientation of the two spin-labeled RNA helices with respect to each other was analyzed with orientation-selective PELDOR and compared to the crystal structure. These results demonstrate for the first time the unique value of the Çm spin label in combination with PELDOR to provide information about conformational flexibilities and orientations of secondary structure elements of biologically relevant RNAs.
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Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Magnesio/química , Riboswitch , Tetraciclina/metabolismo , Secuencia de Bases , Cristalografía por Rayos X , Espectroscopía de Resonancia por Spin del Electrón , Modelos Moleculares , Conformación de Ácido Nucleico , Estabilidad del ARN , Marcadores de SpinRESUMEN
Clinical research has demonstrated the efficacy of injectable opioid treatment for long-term, treatment-refractory opioid-dependent patients. It has been hypothesized that compulsive drug use is particularly associated with neuroplasticity changes in the networks corresponding to withdrawal/negative affect and preoccupation/anticipation rather than binge/intoxication. However, as yet, no study has investigated the effect of long-term opioid treatment on key regions within these networks. Magnetic resonance imaging (MRI) was used to assess brain volumes changes during long-term (approximately 9 years) injectable opioid agonist treatment with diacetylmorphine (DAM) in 22 patients with opioid use disorder. Voxel-based morphometry was applied to detect volumetric changes within the networks of binge/intoxication (ventral/dorsal striatum, globus pallidus and thalamus), withdrawal/negative affect (amygdala and ventral striatum) and preoccupation/anticipation (hippocampus, orbitofrontal and anterior cingulate cortex). The relationships between significant volume changes and features of opioid use disorder were tested using Pearson correlation. Long-term opioid agonist treatment was associated with the enlargement of the right caudate nucleus, which was related to the duration of opioid use disorder. In contrast, reduced volume in the right amygdala, anterior cingulate cortex and orbitofrontal cortex were found that were related to opioid dose, onset of opioid consumption and state anxiety. These findings suggest that long-term opioid agonist treatment is related to structural changes in key brain regions underlying binge/intoxication, withdrawal/negative affect and preoccupation/anticipation, suggesting sustained interaction between these systems.
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Analgésicos Opioides/farmacología , Encéfalo/patología , Sustancia Gris/patología , Trastornos Relacionados con Opioides/patología , Adulto , Amígdala del Cerebelo/patología , Núcleo Caudado/patología , Ansia , Femenino , Giro del Cíngulo/patología , Hipocampo/patología , Humanos , Inyecciones , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Prefrontal/patología , Tálamo/patologíaRESUMEN
BACKGROUND: Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients' views and opinions on the topic and the underlying reasons for this practice. METHODS: The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre. RESULTS: Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often. CONCLUSION: As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment.
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Dependencia de Heroína , Drogas Ilícitas , Analgésicos Opioides/uso terapéutico , Heroína/uso terapéutico , Dependencia de Heroína/tratamiento farmacológico , Humanos , Inyecciones IntramuscularesRESUMEN
BACKGROUND: Retention in care is a prerequisite for successful recovery, especially for a chronic condition like opioid dependence. Though retention varies greatly depending on the different substitution medication and treatment model, treatment retention is used as an indicator of treatment quality and effectiveness of care on a system and individual level. To monitor the overall quality of the Austrian opioid agonist treatment (OAT) system and to monitor patient satisfaction within the system, a new online-based registry called "eSuchmittel" was introduced in Austria at the beginning of 2011. The objective of this study is to analyze retention rates within the Austrian treatment system and to identify patient characteristics associated with retention, using data collected by the substitution registry. METHODS: The complete Austrian sample of 4778 registered patients starting treatment between 1.1.2011 to 31.12.2012 were included in the prospective cohort study using data from the Austrian substitution registry. For the statistical analysis, multivariate Cox Regression and Kaplan-Meier survival analysis were used to evaluate retention in treatment. RESULTS: The retention rate of the total cohort after two years was around 61%. Retention rates were significantly lower for men (exp(B) = .806, 95% CI 0.714-0.908) and significantly higher for patients aged 30 and older (exp(B) = 1.155, 95% CI 1.044-1.279), among patients located in Vienna (exp(B) = 1.439, 95% CI 1.273-1.626) and among patients prescribed oral slow-release morphine (SROM) (exp(B) = 2.141, 95% CI 1.885-2.430). CONCLUSIONS: Average retention in the Austrian system is high in comparison to international retention rates. Nationally, SROM demonstrates higher treatment retention when compared to other available substitution medications. Sociodemographic and regional indicators also contribute to higher retention in care. A systematic monitoring of retention rates within a national registry is an important tool helping to evaluate the quality of care. In this study, the Austrian OAT system proves very high retention in care, an important success criterion.
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Analgésicos Opioides , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Austria , Estudios de Cohortes , Humanos , Masculino , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Estudios ProspectivosRESUMEN
Splicing is an essential and highly regulated process in mammalian cells. We developed a synthetic riboswitch that efficiently controls alternative splicing of a cassette exon in response to the small molecule ligand tetracycline. The riboswitch was designed to control the accessibility of the 3' splice site by placing the latter inside the closing stem of a conformationally controlled tetracycline aptamer. In the presence of tetracycline, the cassette exon is skipped, whereas it is included in the ligand's absence. The design allows for an easy, context-independent integration of the regulatory device into any gene of interest. Portability of the device was shown through its functionality in four different systems: a synthetic minigene, a reporter gene and two endogenous genes. Furthermore, riboswitch functionality to control cellular signaling cascades was demonstrated by using it to specifically induce cell death through the conditionally controlled expression of CD20, which is a target in cancer therapy.
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Empalme Alternativo , Exones , Riboswitch , Empalme Alternativo/efectos de los fármacos , Animales , Antígenos CD20/genética , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/genética , Secuencia de Bases , Muerte Celular/genética , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , Conformación de Ácido Nucleico , Sitios de Empalme de ARN , Estabilidad del ARN , Riboswitch/efectos de los fármacos , Riboswitch/genética , Biología Sintética , Tetraciclina/farmacologíaRESUMEN
This article describes a new form of administration of inhaled prescribed heroin currently under investigation. It underlines the particularity of opioid agonist prescription in jail and presents new perspectives in using psilocybin in addiction medicine treatment. A brief literature review about vaping confirms its interest in quitting cigarette, with a cost of addiction to vaping and recent worrisome reports of chemical pneumonia. Finally, the withdrawal of WHO guidelines on opiates use in pain management, in the context of a suspicion of conflict of interest, underlines the sensible balance between over- and under- prescription of opiates in analgesic treatment.
Cet article montre l'intérêt d'une nouvelle forme d'administration inhalée d'héroïne pharmaceutique actuellement à l'étude. Il sensibilise aux conditions particulières de la prescription d'agonistes opioïdes en milieu carcéral et ressuscite des souvenirs des seventies en reprenant l'exploration scientifique des vertus thérapeutiques de la psilocybine. Même si le vapotage semble être un bon moyen de lâcher la cigarette, les anciens fumeurs ont tendance à s'y accrocher et un risque de pneumonie chimique parfois mortelle vient d'être mis en évidence. Finalement, le retrait de l'OMS de deux directives relatives à l'usage d'opioïdes dans le traitement de la douleur, sur fond de suspicion de conflit d'intérêts, montre l'équilibre délicat entre sur- et sous-prescription des antalgiques opioïdes.
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Conducta Adictiva , Trastornos Relacionados con Opioides , Analgésicos Opioides , Humanos , Manejo del DolorRESUMEN
While uniform isotope labeling of ribonucleic acids (RNA) can simply and efficiently be achieved by in-vitro transcription, the specific introduction of nucleotides in larger constructs is non-trivial and often ineffective. Here, we demonstrate how a medium-sized (67-mer), biocatalytically relevant RNA (hammerhead ribozyme, HHRz) can be formed by spontaneous hybridization of two differently isotope-labeled strands, each individually synthesized by in-vitro transcription. This allows on the one hand for a significant reduction in the number of isotope-labeled nucleotides and thus spectral overlap particularly under magic-angle spinning (MAS) dynamic nuclear polarization (DNP) NMR conditions, on the other hand for orthogonal 13C/15N-labeling of complementary strands and thus for specific investigation of structurally or functionally relevant inter-strand and/or inter-stem contacts. By this method, we are able to confirm a non-canonical interaction due to single-site resolution and unique spectral assignments by two-dimensional 13C-13C (PDSD) as well as 15N-13C (TEDOR) correlation spectroscopy under "conventional" DNP enhancement. This contact is indicative of the ribozyme's functional conformation, and is present in frozen solution irrespective of the presence or absence of a Mg2+ co-factor. Finally, we use different isotope-labeling schemes in order to investigate the distance dependence of paramagnetic interactions and direct metal-ion DNP if the diamagnetic Mg2+ is substituted by paramagnetic Mn2+.
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Coenzimas/química , Espectroscopía de Resonancia Magnética , Manganeso/química , Pliegue del ARN , ARN Catalítico/química , Modelos Moleculares , Hibridación de Ácido NucleicoRESUMEN
BACKGROUND: There is scarce evidence on prevalence of hepatitis C virus (HCV) infection among individuals who are homeless and diagnosed with severe mental illness. We aimed to investigate the prevalence of HCV infection and associated risk factors in a representative sample of adults from At Home study. METHODS: The Vancouver At Home study is part of the At Home/Chez Soi (AH/CS) project-a pragmatic randomized controlled trial of a Housing First intervention among homeless persons with mental illness in five Canadian cities between 2009 and 2013 with a 2-year follow-up period. RESULTS: Of 497 participants, 28% reported positive HCV serostatus. Educational level equal or less than eighth grade (AOR: 2.3, 95% CI: 1.1, 4.8), history of incarceration (AOR: 2.1, 95% CI: 1.2, 3.5), substance dependence (AOR: 2.0, 95% CI: 1.1, 3.7) and injection drug use during one month prior to the recruitment (AOR: 7.8, 95% CI: 4.0, 15.0) were associated with an increased risk of HCV infection. Having a psychotic disorder (AOR: 0.6, 95% CI: 0.3, 1.0) and age < 25 (AOR: 0.2, 95% CI: 0.0, 0.7) were associated with a lower risk. Blood tests performed on 30 participants agreed with self-report in 97% of cases [Kappa = 0.9 (95% CI: 0.6, 1.3), PABAK = 0.9]. CONCLUSION: The high prevalence of HCV among individuals who were homeless with mental illness underlies the importance of prevention and treatment of HCV in this population, especially those with concurrent substance use disorders. Self-report seems to be a valid tool for evaluation of the HCV status in this population.
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Hepatitis C/epidemiología , Personas con Mala Vivienda/estadística & datos numéricos , Trastornos Mentales/epidemiología , Adulto , Colombia Británica/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto JovenRESUMEN
While dynamic nuclear polarization (DNP) under magic-angle spinning (MAS) is generally a powerful method capable of greatly enhancing the sensitivity of solid-state NMR spectroscopy, hyperpolarization also gives rise to peculiar spin dynamics. Here, we elucidate how specific cross-relaxation enhancement by active motions under DNP (SCREAM-DNP) can be utilized to selectively obtain MAS-NMR spectra of an RNA aptamer in a tightly bound complex with a methyl-bearing ligand (tetracycline) due to the effective CH3 -reorientation at an optimized sample temperature of approximately 160â K. SCREAM-DNP can spectrally isolate the complex from non-bound species in an RNA mixture. This selectivity allows for a competition assay between the aptamer and a mutant with compromised binding affinity. Variations in molecular structure and methyl dynamics, as observed by SCREAM-DNP, between free tetracycline and RNA-bound tetracycline are discussed.
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AIMS: Posttraumatic stress disorder (PTSD) is a significant comorbidity in substance use disorders (SUDs). While most studies have addressed trauma/PTSD in abstinent patients, little is known about trauma/PTSD in early detoxification treatment. The current study therefore addresses the systematic evaluation of trauma/PTSD in early inpatient detoxification. METHODS: A cross-sectional survey was accomplished in three German-speaking clinics (n = 134) specialized in inpatient detoxification and motivation treatment. All measures are based on self-report using trauma-specific questionnaires and measures for general psychopathological burden. RESULTS: Participation rate was 60.1% and patients did not show clinically obvious psychological distress during or after assessment. DSM-IV traumatic events were reported by 66.4%. Of the total sample, 38.1% screened positive for PTSD, and 14.9% screened positive for subsyndromal PTSD. PTSD patients reported significantly more childhood adversities and significantly higher scores in depression and -general psychopathology compared to subsyndromal PTSD and SUD-only patients. CONCLUSIONS: Early and systematic evaluation of PTSD in SUD inpatient detoxification treatment is largely safe and yields important information for individual treatment. The high PTSD-rate and the high symptom load in SUD patients during inpatient detoxification treatment highlight the need for a more stringent address of trauma/PTSD in early SUD treatment.
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Diagnóstico Precoz , Pacientes Internos/psicología , Motivación , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Síntomas Prodrómicos , Factores de Riesgo , Suiza/epidemiología , Adulto JovenRESUMEN
Regulation of the expression of nuclear genes encoding chloroplast proteins allows for metabolic adjustment in response to changing environmental conditions. This regulation is linked to retrograde signals that transmit information on the metabolic state of the chloroplast to the nucleus. Transcripts of several APETALA2/ETHYLENE RESPONSE FACTOR transcription factors (AP2/ERF-TFs) were found to respond within 10 min after transfer of low-light-acclimated Arabidopsis thaliana plants to high light. Initiation of this transcriptional response was completed within 1 min after transfer to high light. The fast responses of four AP2/ERF genes, ERF6, RRTF1, ERF104, and ERF105, were entirely deregulated in triose phosphate/phosphate translocator (tpt) mutants. Similarly, activation of MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) was upregulated after 1 min in the wild type but not in the tpt mutant. Based on this, together with altered transcript regulation in mpk6 and erf6 mutants, a retrograde signal transmission model is proposed starting with metabolite export through the triose phosphate/phosphate translocator with subsequent MPK6 activation leading to initiation of AP2/ERF-TF gene expression and other downstream gene targets. The results show that operational retrograde signaling in response to high light involves a metabolite-linked pathway in addition to previously described redox and hormonal pathways.