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1.
BMC Public Health ; 23(1): 1274, 2023 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-37391769

RESUMEN

BACKGROUND: The Inner Santiago Health Study (ISHS) aimed to (i) estimate the prevalence of common mental disorders (CMD; i.e. depressive and anxiety disorders) among immigrants of Peruvian origin in Chile; (ii) determine whether such immigrants are at higher risk of CMD when compared with the native-born geographically matched population (i.e. non-immigrants); and (iii) identify factors associated with higher risk of any CMD among this immigrant group. A secondary aim was to describe access to mental health services by Peruvian immigrants meeting criteria for any CMD. METHODS: Findings are based on a population-based cross-sectional household mental health survey of 608 immigrant and 656 non-immigrant adults (18-64 years) residing in Santiago de Chile. Diagnoses of ICD-10 depressive and anxiety disorders and of any CMD were obtained using the Revised Clinical Interview Schedule. The relationships between demographic, economic, psychosocial, and migration-specific predictor variables, and risk of any CMD were analyzed with a series of stepwise multivariate logistic regression models. RESULTS: The one-week prevalence of any CMD was 29.1% (95% CI: 25.2-33.1) among immigrants and 34.7% (95% CI: 30.7-38.7) among non-immigrants. Depending on the statistical model used in the pooled sample, we found the prevalence of any CMD among non-immigrants to be higher (OR=1.53; 95% CI: 1.05-2.25) or similar (OR=1.34; 95% CI: 0.94-19.2) when compared with immigrants. In the multivariate stepwise regression of any CMD in immigrants only, the prevalence was higher for females, those with primary compared to higher education, in debt and exposed to discrimination. Conversely, higher levels of functional social support, sense of comprehensibility, and manageability were associated with a lower risk of any CMD in immigrants. In addition, no differences were observed between immigrants and non-immigrants reporting any CMD in mental health service utilization. CONCLUSION: Our results evidence high levels of current CMD in this immigrant group, particularly amongst women. However, lower adjusted prevalence of any CMD in immigrants compared to non-immigrants was limited to preliminary statistical models, thus failing to provide clear support for a "healthy immigrant effect". The study sheds new light on differences in CMD prevalence by immigrant status in Latin America by examining differential exposure to risk factors in immigrant versus non-immigrant groups.


Asunto(s)
Trastornos Mentales , Adulto , Humanos , Femenino , Chile/epidemiología , Estudios Transversales , Perú/epidemiología , Trastornos Mentales/epidemiología , Trastornos de Ansiedad
2.
Ecotoxicol Environ Saf ; 268: 115718, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38000305

RESUMEN

Chronic toxicity tests on adult and larval honey bees (Apis mellifera) can require the use of dietary additives (solvents, emulsifiers, adjuvants and viscosifier agents) when the active ingredient of plant protection products cannot be dissolved or does not remain stable and homogeneous within the test diets. Acetone is the widely used and accepted solvent allowed within the international regulatory guidelines, but it can be ineffective in keeping certain compounds in solution and can cause toxicity to adults and larvae. In this publication, we present an evaluation of alternative additives in adult and larval diets. Six dietary additives including five solvents (ethanol, isopropanol, n-propanol, propylene glycol and triethylene glycol) and a viscosifier agent (xanthan gum) at five concentrations along with a negative control and a solvent control (acetone) were investigated at seven laboratories. The safe levels for bees were determined for each of the additives used in the 10-day chronic adult and 22-day chronic larval tests. In the 10-day chronic adult study, ethanol and isopropanol were found to be safe at concentrations ≤ 5.0 %, while xanthan gum can be reliably used at concentrations ≤ 0.1 %. Greater variability across laboratories was observed for N-propanol, propylene glycol, and triethylene glycol and these agents may cause mortality when added to diets at concentrations above 0.25-0.5 %. The safe levels of additives to larval diet in the 22-day chronic larval test had a greater variability and were generally lower than what were observed for adult diet. Our results do not recommend the inclusion of ethanol or n-propanol into the larval diet, and isopropanol, propylene glycol, and triethylene glycol may cause mortality at concentrations above 0.25-0.5 %. Safe levels for xanthan gum were more variable than what was observed for adults, but it can be used reliably at concentrations ≤ 0.05 %. Our analyses conclude that several additives can be integrated successfully in honey bee laboratory bioassays at levels that cause low mortality to adults and larvae.


Asunto(s)
2-Propanol , Acetona , Abejas , Animales , Larva , 1-Propanol , Laboratorios , Dieta , Solventes , Etanol , Glicoles de Propileno
3.
Gesundheitswesen ; 85(10): 878-886, 2023 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-36848946

RESUMEN

BACKGROUND: Sickness-related absences are of particular importance both in the German armed forces and in the civilian sector. THE AIM OF THIS STUDY: was to analyze the incidence of sick leave among soldiers in comparison to the working population covered by the statutory health insurance (SHI) system. METHOD: According to the systematics of the SHI, the key figures on incapacity to work in the period 2008-2018 are calculated in an age- and gender-standardized manner. Likewise, a list of the TOP 20 ICD-10 diagnoses in relation to incapacity to work was determined, and their average annual rates of change were calculated for trend analysis. RESULTS: The annual rate of sick leave among soldiers was between 1.5 and 2.3%, which was lower than that of the SHI (3.1 to 5.0%). The duration of illness (sick days per case) among soldiers was between 9.0-15.6 days per year, compared with 10.9-14.4 days in the SHI system. The sickness frequency (cases per 100 persons) was lower among soldiers (48.2-75.0 cases) than in the SHI (96.8-131.0 cases). Most days of absence among soldiers were due to "respiratory infections (J06)" with 13.2%, "stress reactions (F43)" with 8.7%, "other infectious gastroenteritis and colitis (A09)" with 6.5%, "back pain (M54)" with 4.4% and "depressive episode (F32)" with 4.0% of all days of absence and were comparable to the values in SHI. "Depressive episode (F32)", "injuries (T14)", sreactions (F43)", "respiratory infections (J06)" and "pregnancy complaints (O26)" showed the highest rates of increase of+6.1% to+3.6% of days off work. CONCLUSION: For the first time, it was possible to compare the sickness rate of soldiers with that of the general population in Germany, which may also provide indications for further measures for primary, secondary and tertiary prevention. The lower sickness rate among soldiers compared with the general population is mainly due to a lower incidence of illness, with a similar duration and pattern of illness, but with an overall upward trend. The ICD-10 diagnoses "Depressive episode (F32)," "injuries (T14)," "stress reactions (F43)," "acute upper respiratory tract infections (J06)" and "pregnancy complaints (O26)," which are increasing at an above-average rate in relation to the number of days absent, require further analysis. This approach seems promising, for example, to generate hypotheses and ideas for further improvement of health care.


Asunto(s)
Personal Militar , Infecciones del Sistema Respiratorio , Femenino , Embarazo , Humanos , Ausencia por Enfermedad , Estudios Retrospectivos , Alemania/epidemiología , Seguro de Salud
4.
Appl Microbiol Biotechnol ; 103(1): 505-517, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30415426

RESUMEN

Constructed wetlands (CWs) are well-established wastewater treatment technologies and applied for bioremediation of contaminated water. Despite the optimal performance of CWs, the understanding of the bacterial processes in the rhizosphere, where mainly microbial degradation processes take place, is still limited. In the present study, laboratory-scale CWs planted with Juncus effusus and running under controlled conditions were studied in order to evaluate removal efficiency of dimethylphenols (DMPs), also in comparison to an unplanted bed. Next to removal rates, the bacterial community structure, diversity, and distribution, their correlation with physiochemical parameters, and abundance of the phenol hydroxylase gene were determined. As a result, better removal performance of DMP isomers (3,4-, 3,5-, and 2,6-DMP added as singles compounds or in mixtures) and ammonium loads, together with a higher diversity index, bacterial number, and phenol hydroxylase gene abundance in Juncus effusus CW in comparison with the non-planted CW, indicates a clear rhizosphere effect in the experimental CWs. An enhancement in the DMP removal and the recovery of the phenol hydroxylase gene were found during the fed with the DMP mixture. In addition, the shift of bacterial community in CWs was found to be DMP isomer dependent. Positive correlations were found between the bacteria harboring the phenol hydroxylase gene and communities present with 3,4-DMP and 3,5-DMP isomers, but not with the community developed with 2,6-DMP. These results indicate that CWs are highly dynamic ecosystems with rapid changes in bacterial communities harboring functional catabolic genes.


Asunto(s)
Consorcios Microbianos/fisiología , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/aislamiento & purificación , Humedales , Xilenos/aislamiento & purificación , Biodegradación Ambiental , Biodiversidad , Genes Bacterianos , Isomerismo , Laboratorios , Metabolismo/genética , Oxigenasas de Función Mixta/genética , Poaceae , Análisis Espacio-Temporal , Contaminantes Químicos del Agua/química , Xilenos/química
6.
J Glob Antimicrob Resist ; 38: 154-157, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38908823

RESUMEN

OBJECTIVES: We report the use of IV dalbavancin in Canadian patients using data captured by the national CLEAR registry. METHODS: The CLEAR registry uses the web-based data management program, REDCap™ (online survey https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=TPMWJX98HL) to facilitate clinicians entering details associated with their clinical experiences using IV dalbavancin. RESULTS: Data were available for 40 patients. The most common infections treated were acute bacterial skin and skin structure infection (ABSSSI) (62.5% of patients), bone/joint infection (22.5%), bloodstream/vascular infection (7.5%) and endocarditis (5.0%). Dalbavancin was used as directed (75.0%) and empiric therapy (25.0%). MRSA was the most common identified pathogen (70.0%). Dalbavancin was used both in outpatient (e.g., emergency department) (65.0%), and inpatient treatment settings (e.g., hospital ward) (35.0%). Dalbavancin was used due to the convenience of a single dose treatment (77.5%) as well as to facilitate hospital discharge (7.5%). Dalbavancin was primarily used alone (90.0%), and most commonly using a single 1500 mg dose (77.5%). Microbiological success (pathogen eradicated or presumed eradicated) occurred in 88.2% of known cases, while clinical success (cure and/or improvement) occurred in 93.3% of known cases. No adverse events were reported. CONCLUSIONS: In Canada, IV dalbavancin is used as both directed and empiric therapy to treat ABSSSI as well as off-label (bone/joint, bacteremia/vascular, endocarditis, device-related) infections. It is used in both outpatient and inpatient settings due primarily to its convenience as a single-dose treatment regimen and to facilitate early hospital discharge. Dalbavancin use is associated with high microbiological and clinical cure rates along with an excellent safety profile.


Asunto(s)
Antibacterianos , Sistema de Registros , Teicoplanina , Teicoplanina/análogos & derivados , Teicoplanina/uso terapéutico , Teicoplanina/administración & dosificación , Humanos , Canadá , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano , Adulto , Anciano de 80 o más Años , Administración Intravenosa , Adulto Joven
7.
J Am Chem Soc ; 135(51): 19229-36, 2013 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-24295228

RESUMEN

Efficient charge carrier transport in organic field-effect transistors (OFETs) often requires thin films that display long-range order and close π-π packing that is oriented in-plane with the substrate. Although some polymers have achieved high field-effect mobility with such solid-state properties, there are currently few general strategies for controlling the orientation of π-stacking within polymer films. In order to probe structural effects on polymer-packing alignment, furan-containing diketopyrrolopyrrole (DPP) polymers with similar optoelectronic properties were synthesized with either linear hexadecyl or branched 2-butyloctyl side chains. Differences in polymer solubility were observed and attributed to variation in side-chain shape and polymer backbone curvature. Averaged field-effect hole mobilities of the polymers range from 0.19 to 1.82 cm(2)/V·s, where PDPP3F-C16 is the least soluble polymer and provides the highest maximum mobility of 2.25 cm(2)/V·s. Analysis of the films by AFM and GIXD reveal that less soluble polymers with linear side chains exhibit larger crystalline domains, pack considerably more closely, and align with a greater preference for in-plane π-π packing. Characterization of the polymer solutions prior to spin-coating shows a correlation between early onset nanoscale aggregation and the formation of films with highly oriented in-plane π-stacking. This effect is further observed when nonsolvent is added to PDPP3F-BO solutions to induce aggregation, which results in films with increased nanostructural order, in-plane π-π orientation, and field-effect hole mobilities. Since nearly all π-conjugated materials may be coaxed to aggregate, this strategy for enhancing solid-state properties and OFET performance has applicability to a wide variety of organic electronic materials.

8.
J Virol ; 86(23): 13038-48, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23015698

RESUMEN

Adeno-associated virus (AAV) capsid assembly requires expression of the assembly-activating protein (AAP) together with capsid proteins VP1, VP2, and VP3. AAP is encoded by an alternative open reading frame of the cap gene. Sequence analysis and site-directed mutagenesis revealed that AAP contains two hydrophobic domains in the N-terminal part of the molecule that are essential for its assembly-promoting activity. Mutation of these sequences reduced the interaction of AAP with the capsid proteins. Deletions and a point mutation in the capsid protein C terminus also abolished capsid assembly and strongly reduced the interaction with AAP. Interpretation of these observations on a structural basis suggests an interaction of AAP with the VP C terminus, which forms the capsid protein interface at the 2-fold symmetry axis. This interpretation is supported by a decrease in the interaction of monoclonal antibody B1 with VP3 under nondenaturing conditions in the presence of AAP, indicative of steric hindrance of B1 binding to its C-terminal epitope by AAP. In addition, AAP forms high-molecular-weight oligomers and changes the conformation of nonassembled VP molecules as detected by conformation-sensitive monoclonal antibodies A20 and C37. Combined, these observations suggest a possible scaffolding activity of AAP in the AAV capsid assembly reaction.


Asunto(s)
Proteínas de la Cápside/genética , Cápside/metabolismo , Dependovirus/metabolismo , Ensamble de Virus/genética , Anticuerpos Monoclonales , Cápside/ultraestructura , Proteínas de la Cápside/metabolismo , Dependovirus/ultraestructura , Immunoblotting , Inmunoprecipitación , Microscopía Electrónica , Mutagénesis Sitio-Dirigida , Estructura Terciaria de Proteína , Análisis de Secuencia de ADN
9.
Proc Natl Acad Sci U S A ; 107(22): 10220-5, 2010 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-20479244

RESUMEN

The volume available in icosahedral virus capsids limits the size of viral genomes. To overcome this limitation, viruses have evolved strategies to increase their coding capacity by using more than one ORF while keeping the genome length constant. The assembly of virus capsids requires the coordinated interaction of a large number of subunits to generate a highly ordered structure in which the viral genome can be enclosed. To understand this process, it is essential to know which viral and nonviral components are involved in the assembly reaction. Here, we show that the adeno-associated virus (AAV) encodes a protein required for capsid formation by means of a nested, alternative ORF of the cap gene. Translation is initiated at a nonconventional translation start site, resulting in the expression of a protein with a calculated molecular weight of 23 kDa. This protein, designated assembly-activating protein (AAP), is localized in the host cell nucleolus, where AAV capsid morphogenesis occurs. AAP targets newly synthesized capsid proteins to this organelle and in addition fulfils a function in the assembly reaction itself. Sequence analysis suggests that also all other species of the genus Dependovirus encode a homologous protein in their cap gene. The arrangement of different ORFs that encode capsid proteins and an assembly factor within the same mRNA facilitates a timely coordinated expression of the components involved in the assembly process.


Asunto(s)
Cápside/fisiología , Nucléolo Celular/virología , Dependovirus/fisiología , Ensamble de Virus/fisiología , Secuencia de Aminoácidos , Secuencia de Bases , Proteínas de la Cápside/genética , Proteínas de la Cápside/fisiología , Línea Celular , Cartilla de ADN/genética , ADN Viral/genética , Dependovirus/genética , Expresión Génica , Genes Virales , Prueba de Complementación Genética , Células HeLa , Humanos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico
10.
Artículo en Inglés | MEDLINE | ID: mdl-37022871

RESUMEN

MRI-compatible robots provide a means of studying brain function involved in complex sensorimotor learning processes, such as adaptation. To properly interpret the neural correlates of behavior measured using MRI-compatible robots, it is critical to validate the measurements of motor performance obtained via such devices. Previously, we characterized adaptation of the wrist in response to a force field applied via an MRI-compatible robot, the MR-SoftWrist. Compared to arm reaching tasks, we observed lower end magnitude of adaptation, and reductions in trajectory errors beyond those explained by adaptation. Thus, we formed two hypotheses: that the observed differences were due to measurement errors of the MR-SoftWrist; or that impedance control plays a significant role in control of wrist movements during dynamic perturbations. To test both hypotheses, we performed a two-session counterbalanced crossover study. In both sessions, participants performed wrist pointing in three force field conditions (zero force, constant, random). Participants used either the MR-SoftWrist or the UDiffWrist, a non-MRI-compatible wrist robot, for task execution in session one, and the other device in session two. To measure anticipatory co-contraction associated with impedance control, we collected surface EMG of four forearm muscles. We found no significant effect of device on behavior, validating the measurements of adaptation obtained with the MR-SoftWrist. EMG measures of co-contraction explained a significant portion of the variance in excess error reduction not attributable to adaptation. These results support the hypothesis that for the wrist, impedance control significantly contributes to reductions in trajectory errors in excess of those explained by adaptation.

11.
Can J Hosp Pharm ; 76(4): 309-313, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767389

RESUMEN

Background: Among critically ill patients receiving mechanical ventilation, Candida spp. are commonly detected in the lower respiratory tract (LRT). This is generally considered to represent colonization. Objective: To evaluate the use of antifungal treatments and the clinical outcomes of patients with Candida colonization of the LRT. Methods: This retrospective analysis involved consecutive patients admitted to the intensive care unit between April 2016 and May 2021with positive results on Candida spp. testing of LRT samples. Data related to antifungal treatment and clinical outcomes were analyzed descriptively, and multivariable logistic regression was performed. Results: Of 200 patients initially identified, 160 (80%) died in hospital. Antifungal therapy was given to 103 (51.5%) of the patients, with treatment being more likely among those with shock and those who received parenteral nutrition. Mortality was high among patients with positive Candida results on LRT culture, regardless of treatment. Multivariable logistic regression, with adjustment for age, sex, comorbidities, and sequential organ failure assessment (SOFA) score, showed that antifungal treatment was associated with lower odds of death (odds ratio 0.39, 95% confidence interval 0.17-0.87) compared with no treatment (p = 0.021). Conclusions: This study showed higher mortality rates than have been reported previously. Further investigation into the role of antifungal therapy among critically ill patients with Candida spp. colonization is required.


Contexte: Chez les patients gravement malades recevant une ventilation mécanique, les Candida spp. sont fréquemment détectées dans les voies respiratoires inférieures (VRI) ­ une situation généralement considérée comme une colonisation. Objectif: Évaluer l'utilisation d'un traitement antifongique et les résultats cliniques chez les patients présentant une colonisation par Candida dans les VRI. Méthodes: Cette analyse rétrospective portait sur des patients consécutifs de l'unité de soins intensifs ayant obtenu un résultat positif au test de Candida sur les isolats des VRI entre avril 2016 et mai 2021. Les données relatives au traitement antifongique et aux résultats cliniques ont été analysées de manière descriptive, et une régression logistique multivariable a été effectuée. Résultats: Parmi les 200 patients initialement recensés, 160 (80 %) sont décédés à l'hôpital. Une thérapie antifongique a été administrée à 103 (51,5 %) des patients, et le traitement était plus probable chez ceux en état de choc et ceux ayant reçu une nutrition parentérale. Les patients ayant été déclarés positifs pour la Candida dans la culture des VRI présentaient un taux de mortalité élevé, indépendamment du traitement. Une régression logistique multivariable, avec ajustement pour l'âge, le sexe, les comorbidités et le score SOFA (sequential organ failure assessment), a montré que le traitement antifongique était associé à une probabilité de décès réduite (rapport de cotes 0,39; intervalle de confiance à 95 % 0,17­0,87), par rapport à l'absence de traitement (p = 0,021). Conclusions: Cette étude a révélé des taux de mortalité plus élevés que ce qui avait été rapporté précédemment. Une enquête plus approfondie sur le rôle de la thérapie antifongique chez les patients gravement malades présentant une colonisation par Candida spp. est nécessaire.

12.
PeerJ ; 11: e15870, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37692110

RESUMEN

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Terremotos , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Trastornos por Estrés Postraumático , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Chile/epidemiología , Prevalencia , Trastornos por Estrés Postraumático/epidemiología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética
13.
J Am Chem Soc ; 134(6): 2884-7, 2012 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-22276735

RESUMEN

Solution deposition using high-boiling-point additives such as octanedithiol (ODT) provides a simple and widely used fabrication option for improving the power conversion efficiencies of solar cells composed of narrow-band-gap conjugated polymer donor/fullerene acceptor blends. Previous examination of the resulting device active layers has shown that the use of additives influences the degree of phase segregation within the bulk heterojunction (BHJ) blend and also improves ordering within the polymeric domains. In this work, in situ grazing-incidence wide-angle X-ray scattering as a function of time was used to explore the dynamics of the BHJ evolution. These studies showed that a small percentage of ODT in chlorobenzene (CB) induced the nucleation of polymeric crystallites within 2 min of deposition, increased the orientational order of specific polymorphs, and promoted further crystallite nucleation over a period longer than 40 min after casting. Similar structural changes did not occur when the same BHJ blend was cast from pure CB.

14.
J Gen Virol ; 93(Pt 9): 1887-1898, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22694902

RESUMEN

Adeno-associated virus (AAV) capsid assembly occurs in the nucleus. Newly synthesized capsid proteins VP1, VP2 and VP3 contain several basic regions (BRs), which may act as nuclear localization signals (NLSs). Mutation of BR2 and BR3, located at the VP1 and VP2 N termini, marginally reduced nuclear uptake of VP1 or VP2, but not of VP3, when expressed in the context of the whole AAV type 2 (AAV2) genome. Combined mutation of BR1, BR2 and BR3 resulted in capsids with slightly reduced amounts of VP1. Expression of isolated VP1/2 N termini revealed an influence of BR3 on nuclear transport, whilst BR1 or BR2 had no effect. However, deletion of an N-terminal fragment in front of the BR elements strongly reduced nuclear uptake of VP1/2 N termini. Mutation of BR4, present in all three capsid proteins, led to their retention in the cytoplasm and to the formation of speckles, resulting in a lack of capsid formation and a significant reduction in VP levels. In a VP fragment comprising BR2, BR3 and BR4, the BR4 element was not necessary for nuclear localization. Mutation of BR5 in the C-terminal part of the VPs resulted in a speckled protein distribution in the nucleus, strongly reduced capsid assembly, and low VP1 and VP2 levels. Taken together, these results showed that BR2 and BR3 have a weak influence on nuclear transport of VP1 and VP2, whilst combined mutation of BR1, BR2 and BR3 influences the stoichiometry of VPs in assembled capsids. BR4 and BR5 play a crucial role in capsid assembly but have no NLS activity.


Asunto(s)
Proteínas de la Cápside/metabolismo , Núcleo Celular/virología , Dependovirus/fisiología , Infecciones por Parvoviridae/virología , Virión/fisiología , Ensamble de Virus , Transporte Activo de Núcleo Celular , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Núcleo Celular/metabolismo , Dependovirus/química , Dependovirus/genética , Datos de Secuencia Molecular , Señales de Localización Nuclear , Infecciones por Parvoviridae/metabolismo , Alineación de Secuencia , Virión/química , Virión/genética
15.
J Psychiatr Res ; 145: 284-293, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33199052

RESUMEN

Mindfulness-based Stress Reduction (MBSR) has shown good efficacy for improving wellbeing in employees experiencing occupational stress. However, comparisons with other interventions, longer-term follow-up, and data from varying sociocultural contexts are lacking. This three-arm, parallel randomised controlled trial (RCT) examined the effects of MBSR on psychological distress in non-physician health workers in direct contact with patients. 105 participants were randomly allocated to either: (1) MBSR (N = 35), (2) Stress Management Course (SMC; N = 34) or (3) wait-list (N = 36). Participants and those assessing outcomes were blinded to group assignment. Participants completed questionnaires pre- and post-intervention and four months after the intervention. Psychological distress was measured using the General Health Questionnaire (GHQ-12) and Outcome Questionnaire (OQ-45). Secondary outcomes included perceived stress, job satisfaction, mindfulness skills and changes in salivary cortisol. 77 participants completed measures post-intervention and 52 at 4-month follow-up. MBSR showed a post-intervention effect in reducing GHQ-12 (ß = -0.80 [SE = 1.58] p < 0.01) and OQ-45 (ß = -0.72, [SE = 5.87] p < 0.05) psychological distress, compared to SMC and in reducing GHQ-12 (ß = -1.30 [SE = 1.38] p < 0.001) and OQ-45 (ß = -0.71, [SE = 5.58] p < 0.01) psychological distress compared to wait-list condition. In our secondary outcome, only MBSR was associated with a decrease in the cortisol awaking response by 23% (p < 0.05). At follow-up, only effects of MBSR on the psychological distress 'social role' subscale (ß = -0.76 [SE = 1.31] p < 0.05) remained significant, compared to SMC. In conclusion, MBSR appears useful in reducing short-term psychological distress in healthcare workers, but these effects were not maintained at follow-up. Trial registration: ISRCTN12039804.


Asunto(s)
Atención Plena , Distrés Psicológico , Personal de Salud , Humanos , Estrés Psicológico/psicología , Estrés Psicológico/terapia , Encuestas y Cuestionarios , Resultado del Tratamiento
16.
J Occup Environ Med ; 62(11): 937-942, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32804746

RESUMEN

OBJECTIVE: This study examined the relationship between job insecurity and presenteeism, and the role of workplace health promotion as moderator in this association. METHODS: We used data from 9525 employees from the sixth BIBB/BAuA Employment Survey 2012 for the working population in Germany. Data analysis was performed with logistic regressions. RESULTS: Job insecurity was associated with a higher risk of presenteeism, even after adjustment for control factors (OR = 1.25, CI: 1.01-1.53, P < 0.05). Workplace health promotion moderated this relationship: It no longer existed in companies with health promotion. CONCLUSIONS: The results suggest that employees with job insecurity are more likely to work despite feeling ill with the aim of securing their jobs. By establishing workplace health promotion, companies can protect their employees from that behavior in order to avoid negative long-term consequences.


Asunto(s)
Promoción de la Salud , Presentismo , Lugar de Trabajo , Empleo , Alemania , Humanos
17.
Front Immunol ; 11: 602868, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33343574

RESUMEN

A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström's macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88L252P mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88L252P-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88L252P mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88L252P mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM.


Asunto(s)
Linfocitos B/metabolismo , Marcación de Gen , Inmunoglobulina M/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Factor 88 de Diferenciación Mieloide/genética , Células Plasmáticas/metabolismo , Mutación Puntual , Animales , Linfocitos B/inmunología , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Predisposición Genética a la Enfermedad , Inmunoglobulina M/inmunología , Activación de Linfocitos , Ratones Endogámicos C57BL , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Paraproteínas/metabolismo , Fenotipo , Células Plasmáticas/inmunología
18.
Nat Mater ; 7(2): 142-5, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18037892

RESUMEN

Block copolymers consisting of incompatible components self-assemble into microphase-separated domains yielding highly regular structures with characteristic length scales of the order of several tens of nanometres. Therefore, in the past decades, block copolymers have gained considerable potential for nanotechnological applications, such as in nanostructured networks and membranes, nanoparticle templates and high-density data storage media. However, the characteristic size of the resulting structures is usually determined by molecular parameters of the constituent polymer molecules and cannot easily be adjusted on demand. Here, we show that electric d.c. fields can be used to tune the characteristic spacing of a block-copolymer nanostructure with high accuracy by as much as 6% in a fully reversible way on a timescale in the range of several milliseconds. We discuss the influence of various physical parameters on the tuning process and study the time response of the nanostructure to the applied field. A tentative explanation of the observed effect is given on the basis of anisotropic polarizabilities and permanent dipole moments of the monomeric constituents. This electric-field-induced effect further enhances the high technological potential of block-copolymer-based soft-lithography applications.

19.
Traffic Inj Prev ; 20(6): 607-612, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31283362

RESUMEN

Objective: As vehicle safety technologies and evaluation procedures advance, it is pertinent to periodically evaluate injury trends to identify continuing and emerging priorities for intervention. This study examined detailed injury distributions and injury risk trends in belted occupants in frontal automobile collisions (10 o'clock to 2 o'clock) using NASS-CDS (1998-2015). Methods: Injury distributions were examined by occupant age and vehicle model year (stratified at pre- and post-2009). Logistic regression models were developed to examine the effects of various factors on injury risk (by body region), controlling for delta-V, sex, age, height, body mass index (BMI), vehicle model year (again stratified at 2009). Results: Among other observations, these analyses indicate that newer model year vehicles (model year [MY] 2009 and later) carry less risk of Abbreviated Injury Scale (AIS) 2+ and AIS 3+ injury compared to older model year vehicles, with odds ratios of 0.69 (AIS 2+) and 0.45 (AIS 3+). The largest reductions in risk between newer model year vehicles and older model year vehicles occur in the lower extremities and in the risk of skull fracture. There is no statistically significant change in risk of AIS 3+ rib fracture or sternum injury between model year categories. Females are at greater risk of AIS 2+ and AIS 3+ injury compared to males, with increased risk across most injury types. Conclusions: For belted occupants in frontal collisions, substantial reductions in injury risk have been realized in many body regions in recent years. Risk reduction in the thorax has lagged other body regions, resulting in increasing prevalence among skeletal injuries in newer model year vehicles (especially in the elderly). Injuries also remain common in the arm and hand/wrist for all age ranges studied. These results provide insight into where advances in the field have made gains in occupant protection and what injury types remain to be addressed.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Cinturones de Seguridad/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Escala Resumida de Traumatismos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vehículos a Motor/estadística & datos numéricos , Estados Unidos/epidemiología , Adulto Joven
20.
Sci Adv ; 2(3): e1501571, 2016 03.
Artículo en Inglés | MEDLINE | ID: mdl-27051870

RESUMEN

Correlating spatial chemical information with the morphology of closely packed nanostructures remains a challenge for the scientific community. For example, supramolecular self-assembly, which provides a powerful and low-cost way to create nanoscale patterns and engineered nanostructures, is not easily interrogated in real space via existing nondestructive techniques based on optics or electrons. A novel scanning probe technique called infrared photoinduced force microscopy (IR PiFM) directly measures the photoinduced polarizability of the sample in the near field by detecting the time-integrated force between the tip and the sample. By imaging at multiple IR wavelengths corresponding to absorption peaks of different chemical species, PiFM has demonstrated the ability to spatially map nm-scale patterns of the individual chemical components of two different types of self-assembled block copolymer films. With chemical-specific nanometer-scale imaging, PiFM provides a powerful new analytical method for deepening our understanding of nanomaterials.


Asunto(s)
Microscopía de Fuerza Atómica/métodos , Nanoestructuras/química , Modelos Químicos , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier
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