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1.
J Neurosci Res ; 101(4): 448-463, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36546658

RESUMO

The pathophysiology of early-onset torsion dystonia (TOR1A/DYT1) remains unclear. Like 70% of human mutation carriers, rodent models with ΔGAG mutation such as DYT1 knock-in (KI) mice do not show overt dystonia but have subtle sensorimotor deficits and pattern of abnormal synaptic plasticity within the striatal microcircuits. There is evidence that dysfunction of striatal parvalbumin-reactive (Parv+) fast-spiking interneurons (FSIs) can be involved in dystonic signs. To elucidate the relevance of these GABAergic interneurons in the pathophysiology of DYT1 dystonia, we used in vivo optogenetics to specifically inhibit Parv+ and to detect changes in motor behavior and neuronal activity. Optogenetic fibers were bilaterally implanted into the dorsal striatum of male DYT1 KI mice and wild-type (WT) littermates expressing halorhodopsin (eNpHR3.0) in Parv+ interneurons. While stimulations with yellow light pulses for up to 60 min at different pulse durations and interval lengths did not induce abnormal movements, such as dystonic signs, immunohistochemical examinations revealed genotype-dependent differences. In contrast to WT mice, stimulated DYT1 KI showed decreased striatal neuronal activity, that is, less c-Fos reactive neurons, and increased activation of cholinergic interneurons after optogenetic inhibition of Parv+ interneurons. These findings suggest an involvement of Parv+ interneurons in an impaired striatal network in DYT1 KI mice, but at least short-term inhibition of these GABAergic interneurons is not sufficient to trigger a dystonic phenotype, similar to previously shown optogenetic activation of cholinergic interneurons.


Assuntos
Distonia , Humanos , Camundongos , Masculino , Animais , Distonia/genética , Optogenética , Parvalbuminas , Camundongos Transgênicos , Neurônios/metabolismo , Interneurônios/fisiologia , Corpo Estriado/metabolismo , Genótipo , Colinérgicos , Modelos Animais de Doenças , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo
2.
BMC Med Res Methodol ; 23(1): 17, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647023

RESUMO

BACKGROUND: Ensuring motivated and successful study participation is a key challenge in the design and conduct of health research studies. Previously, recruitment barriers and facilitators have been identified mainly from experience, and rarely based on theoretical approaches. We developed a framework of intentional and actional components of engaged participation in public health research studies (INTACT-RS), informed by psychological behavioral models. We aimed a) to identify precise indicators for each framework component and b) to better understand which components and decision processes are essential for study participants. METHODS: Within a multicenter research network, we applied various approaches to recruit parents of newborns, pediatricians, and midwives. All recruitment processes were documented from the perspective of both participants and researchers. We used different qualitative and quantitative data material, which we applied in a multistage process according to the basic principles of qualitative content analysis. RESULTS: INTACT-RS encompasses pre-intentional, intentional and actional phases with a total of n = 15 components covering all aspects of an individual's involvement with a research study. During intention formation, an understanding of efforts and benefits, why participation is valuable beyond contributing to research, and how others perceive the study, were particularly important to (potential) participants. Subsequently (intentional phase), participants consider how and when participation is compatible with their own resources, ability and availability, and hence seek for close communication with, and flexibility and support from the research team. During and after (initial) participation (actional phase), participants' assessment of whether expectations and interests have been met impact crucial further steps, especially the willingness to continue and to recommend participation to others. A strong topic-wise and or supportive participation interest as well as active, continuous exchange with the researchers appeared to be central determinants of study completion and data validity. CONCLUSIONS: A theoretical framework is now available to plan and conduct recruitment of different target groups, which accounts for essential motivational and volitional decision-making processes. Based on empirically specified constructs, possible barriers can be addressed even before the initial recruitment process. Therefore, recommendations for scientific practice have been formulated.


Assuntos
Comunicação , Saúde Pública , Recém-Nascido , Humanos , Motivação , Pesquisa Qualitativa
3.
BMC Pregnancy Childbirth ; 22(1): 717, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127645

RESUMO

BACKGROUND: For quality-oriented evaluation of prenatal and obstetric care, it is important to systematically consider the perspective of the women receiving care in order to comprehensively assess and optimize quality in a woman-centered manner. Empathy and Shared Decision Making (SDM) are essential components of woman-centered midwifery care. The aim of the study was to analyze measurement invariance of the items of the Consultation and Relational Empathy (CARE) and Shared Decision Making-Questionnaire (SDM-Q-9) scales depending on the prenatal versus obstetric care setting. METHODS: One hundred fifty women retrospectively assessed aspects of woman-centered midwifery care in both prenatal and obstetric care setting. The birth of the child was a maximum of 12 months ago. A structural equation modelling approach was adopted to separate true effects from response shift (RS) effects depending on care setting. The latter were analyzed in terms of recalibration (changing women's internal measurement standards), Reprioritization (changing associations of items and construct) as well as Reconceptualization (redefining the target construct). RESULTS: A response shift model was identified for both assessments (pregnancy/birth: CFI = .96/.96; SRMR = .046/.051). At birth, both scales indicated lower quality of care compared with prenatal care (SDM-Q-9-M/CARE-8-M:|d| = 0.190/0.392). Although no reconceptualization is required for the items of both scales, RS effects are evident for individual items. Due to recalibration and reprioritization effects, the true differences in the items are partly underestimated (SDM-Q-9-M/CARE-8-M: 3/2 items) or overestimated (4/2 items). CONCLUSION: The structure of the constructs SDM and Empathy, indicating woman-centered midwifery care, are moderated by the care settings. To validly assess midwives' empathy and shared decision making from women's perspective, setting-dependent response shift effects have to be considered. The proven item-specific response effects contribute to a better understanding of construct characteristics in woman-centered care by midwives during pregnancy and childbirth.


Assuntos
Tomada de Decisão Compartilhada , Tocologia , Criança , Tomada de Decisões , Empatia , Feminino , Humanos , Recém-Nascido , Participação do Paciente , Gravidez , Estudos Retrospectivos , Vitaminas
4.
Anal Bioanal Chem ; 412(28): 7777-7787, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32939566

RESUMO

The continuous measurement of multiple neurotransmitters in microdialysate of freely moving mice to study neurochemical changes in specific brain regions requires a rapid and very sensitive quantitative analytical method. The quantitative analysis of 11 neurotransmitters and metabolites, including serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), melatonin (ME), dopamine (DA), levodopa (L-DOPA), 3-methoxytyramine (3-MT), norepinephrine (NE), epinephrine (EP), acetylcholine (ACh), choline (Ch), and γ-aminobutyric acid (GABA), was performed using a biphenyl column coupled to an API-QTrap 3200 (AB SCIEX) mass spectrometer in positive electrospray ionization mode. To the microdialysate samples, 0.5 ng of isotopically labeled standard was added for analyte quantification. A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous analysis of monoamines, their precursor, and metabolites, as well as ACh, Ch, and GABA in murine microdialysate within 7.0 min. The limit of detection in artificial CSF ranged from 0.005 ng/mL (ME) to 0.75 ng/mL (NE and GABA). A comprehensive pre-analytical protocol was validated. Recovery was between 87 and 117% for neurotransmitter concentrations from 0.6 to 45 ng/mL with an inter-day accuracy of below 20%. Basal neurotransmitter values were determined in the striatum of mice over a time period of 3 h. This LC-MS/MS method, including a short and gentle sample preparation, is suitable for simultaneous measurements of neurotransmitters in murine cerebral microdialysate and enables the determination of basal neurotransmitter levels in specific brain regions to detect disease-related and drug-induced neurochemical changes.Graphical abstract.


Assuntos
Cromatografia Líquida/métodos , Microdiálise , Neurotransmissores/análise , Espectrometria de Massas em Tandem/métodos , Animais , Corpo Estriado/metabolismo , Limite de Detecção , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Reprodutibilidade dos Testes
5.
Gesundheitswesen ; 82(3): 267-273, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-31671455

RESUMO

BACKGROUND: The WHO strategy for active aging comprises maintenance of health, participation in social life as well as integration and social security for the aged. As a political framework for action, the strategy supports the future aging policy of municipalities. This survey examines how local actors assess the WHO strategy of active aging. METHODS: The study consists of 5 guided interviews of experts from the rural district of Constance. The interview was based on a previously coordinated list of indicators that summarize 102 recommendations for action. The awareness of the WHO strategy as well as a brief introduction to the 3 main areas provided the start of the interviews, followed by the comparison of municipal activities with the list of indicators, the identification of the need for action and of previous unrecognized aspects. In the sense of a data triangulation, we conducted a quantitative survey in further districts. The data of the interviews were analyzed by using the method of Gläser and Laudel, referred to as qualitative content analysis. RESULTS: None of the interviewed experts knew the WHO strategy of active aging. However, after a short explanation of the WHO strategy and indicator list, they classified the strategy as practicable. All of them rated the recommendations for action from the sub-areas of participation in society (e.g. creation of advisory councils for seniors) and security in public space and transport (e.g. protection measures for older pedestrians) as feasible. In some areas, such as medical care and formal care, they missed indicators. Hence, we recommend adding new recommendations for action. DISCUSSION: The awareness of local authorities regarding the WHO strategy of active aging should be improved. Taking into account the specified further development needs, active aging is a viable orientation aid and offers several opportunities for aging policy for municipalities.


Assuntos
Atividades Cotidianas , Envelhecimento , População Rural , Organização Mundial da Saúde , Atitude Frente a Saúde , Alemanha , Humanos , Inquéritos e Questionários
6.
Rehabilitation (Stuttg) ; 59(5): 303-314, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31962348

RESUMO

Rehabilitation is evidenced based if treatments are applied that proved to enhance rehabilitation outcomes - generally patients' health or participation- effectively in a causal manner. Randomized control trials (RCTs) allow determining the efficacy of treatments unambiguously. If alternative research designs (e. g. case-control studies, cohort studies, observational studies) are adopted, the association of the treatment and the improvement of the health status or participation may be biased by confounding variables (limitations of internal validity). Several variants of the basic RCT designs have been developed (e. g. cluster-randomized trials, factorial designs, pragmatic trials) to adapt RCTs to the demands of practical applications. Additionally, deciding and acting evidence-based requires rehabilitation treatments and recommendations which have been developed on a solid theoretical basis and which are applied in practical rehabilitation care appropriately. Especially, because treatments have to be chosen and provided according to rehabilitation patients' individual needs. Furthermore, in every day care the application of treatments has to be matched to the specific conditions of the respective rehabilitation institution. Thus, a comprehensive understanding of evidence requires not only efficacy studies adopting RCTs. Additionally, knowledge about treatment efficacy has to be complemented by studies investigating conceptual and theoretical foundations of effective treatments (intervention design) as well as studies to apply treatments in practical rehabilitation care (implementation research) appropriately.


Assuntos
Medicina Baseada em Evidências , Ciência da Implementação , Ensaios Clínicos Controlados Aleatórios como Assunto , Causalidade , Alemanha , Humanos , Projetos de Pesquisa , Resultado do Tratamento
8.
Sex Abuse ; 29(6): 519-540, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26489799

RESUMO

This study examined the association of social anxiety, loneliness, and problematic Internet use (PIU) with the online solicitation of minors. Within a convenience sample of adult Internet users from Germany, Finland, and Sweden ( N = 2,828), we compared the responses of participants who had not interacted sexually with strangers online ( n = 2,049) with participants who sexually interacted with unknown adults online ( n = 642), and both groups with adults who sexually solicited unknown minors online ( n = 137). Online sexual interaction with adults was associated with higher levels of social anxiety, loneliness, and PIU compared with not sexually interacting with strangers online. Sexually soliciting minors online was associated with higher levels of social anxiety, loneliness, and PIU compared with sexually interacting with adults and not sexually interacting with strangers at all. Interestingly, compared with those with adult contacts, loneliness was specifically pronounced for participants who solicited children, whereas social anxiety and PIU were pronounced for participants soliciting adolescents. These findings suggest that social anxiety, loneliness, and PIU may be among the motivators for using the Internet to solicit individuals of different age groups for sexual purposes. These factors emerged as specifically relevant for adults who sexually solicited minors and who reported greater impairments compared with adults who sexually interacted with adults. These characteristics may thus be important to consider for assessment and treatment procedures for individuals soliciting minors online.


Assuntos
Ansiedade/psicologia , Abuso Sexual na Infância/psicologia , Criminosos/psicologia , Internet , Solidão/psicologia , Fobia Social/psicologia , Adolescente , Adulto , Idoso , Ansiedade/diagnóstico , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Fobia Social/diagnóstico , Escalas de Graduação Psiquiátrica , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-38873232

RESUMO

Shifting midwifery education to a university level is of great importance for healthcare systems worldwide by preparing graduates for current and future challenges. Some of them referring to management, research and teaching tasks as well as advanced practitioner roles, require competences that can only be acquired in a Master's program. The objectives of this narrative review are to outline the differences and commonalities of organizational aspects of Master's programs in selected OECD countries and to point out the competence goals and learning outcomes they are based on. Fifteen Master's programs in twelve OECD countries were identified and analyzed. Considering the organizational characteristics, differences are found in admission requirements and qualification levels, while similarities relate to the awarded title (MSc). All programs aim to develop abilities for research to advance midwifery practice. Leadership and management abilities are addressed through effective teamwork and communication. The programs' aims are to develop abilities for midwifery education tasks. Whereas competence goals mostly align across the programs, they are addressed differently through various learning outcomes. Development and enhancement of Master's programs in midwifery are needed by focusing on core elements, such as common competence goals. It is equally important to adapt them to national healthcare and educational systems.

10.
Front Psychol ; 14: 1143110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37284468

RESUMO

Introduction: Interprofessional collaboration of physicians and midwives is essential for appropriate and safe care of pregnant and parturient women as well as their newborns. The complexity of woman-centered care settings requires the continuous exchange of information and the coordinated implementation of multi-and interprofessional care concepts. To analyze the midwives' perspective on the multi-and interprofessional care process during pregnancy, birth and postpartum period, we aimed to adapt and psychometrically evaluate the Interprofessional Collaboration Scale (ICS). Methods: The ICS (13 items) was answered by 299 midwives for (i) prenatal and postpartum care as well as (ii) perinatal care. Three items on equitable communication (EC) identified in qualitative interviews with N = 6 midwives were added as further aspects of quality in collaborative midwifery care. Confirmatory factor analysis was used to test competing theoretically hypothesized factorial model structures, including both care settings simultaneously, i.e., birth and prenatal/postpartum. Results: A two-dimensional structure assuming the 13 original ICS items and the 3 items on EC as psychometric distinct item groups accounts for the data best. After deleting 5 ICS items with insufficient indicator reliability, a very good-fitting model structure was obtained for both prenatal/postpartum as well as perinatal care: χ2df = 192 = 226.35, p = 0.045, CFI = 0.991, RMSEA = 0.025 (90%CI: [0.004; 0.037]). Both the reduced ICS-R and the EC scale (standardized response mean = 0.579/1.401) indicate significantly higher interprofessional collaboration in the birth setting. Responsibility in consulting, attitudes toward obstetric care and frequency of collaboration with other professional groups proved to be associated with the ICS-R and EC scale as expected. Discussion: For the adapted ICS-R and the EC scale a good construct validity could be confirmed. Thus, the scales can be recommended as a promising assessment for recording the collaboration of midwives with physicians working in obstetric care from the perspective of midwives. The instrument provides a validated assessment basis in midwifery and obstetric care to identify potentially divergent perspectives within interprofessional care teams in woman's centered care.

11.
Talanta ; 253: 123965, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208557

RESUMO

The sensitive and simultaneous measurement of multiple neurotransmitters in microdialysate (MD) of freely moving mice is a prerequisite to study neurochemical imbalances in specific brain regions. The quantitative analysis of 16 neurotransmitters and metabolites, including serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), melatonin (ME), dopamine (DA), levodopa (l-DOPA), 3-methoxytyramine (3-MT), norepinephrine (NE), epinephrine (EP), homovanillinic acid (HVA), acetylcholine (ACh), deoxy carnitine (iso-ACh), choline (Ch), and É£-aminobutyric acid (GABA), adenosine (ADE), glutamine (Gln), and glutamic acid (Glu) was achieved within a chromatographic separation time of 6.5 min by the application of a biphenyl column coupled to an API-QTrap 5500 (AB SCIEX) mass spectrometer. Optimized chromatographic separation as well as high sensitivity allow the simultaneous analysis and precise quantification of 16 neurotransmitters and metabolites in artificial cerebrospinal fluid (CSF). Sample preparation procedure consisted of simply adding isotopically labeled internal standard solution to the microdialysis sample. The limits of detection in aCSF ranged from 0.025 pg (Ch) to 9.75 pg (Gln) and 85.5 pg (HVA) on column. Recoveries were between 83 and 111% for neurotransmitter concentrations from 0.6 to 45 ng/ml or 200 ng/ml with a mean intra-day and inter-day coefficient of variation of 7.6% and 11.2%, respectively. Basal extracellular concentrations of the following analytes: 5-HT, 5-HIAA, ME, DA, 3-MT, HVA, ACh, iso-ACh, Ch, GABA, ADE, Gln, and Glu were determined in the striatum of mice with a MD flow rate of 0.5 µl/min. This LC-MS/MS method leads to an accurate quantification of ACh and its isobaric structure iso-ACh, which were detected in the MD samples at ratios of 1:8.6. The main advantage of the high sensitivity is the miniaturization of the MD protocol with short sample collection times and volumes down to 5 µl, which makes this method suitable for pharmacological intervention and optogenetic studies to detect neurochemical changes in vivo.


Assuntos
Serotonina , Espectrometria de Massas em Tandem , Animais , Camundongos , Cromatografia Líquida , Neurotransmissores , Ácido gama-Aminobutírico
12.
Eur J Midwifery ; 7: 22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664000

RESUMO

INTRODUCTION: The acquisition of academic competencies is one of the main outcomes of the academization of midwifery education. To analyze midwives' views on the key academic competencies of the recently reformed midwifery education in Germany, an existing assessment instrument was adapted to the German context of care and psychometrically analyzed. Furthermore, it was investigated whether the relevance assessments of academic and non-academic midwives differ from each other. METHODS: The study design was cross-sectional. A total of 193 (prospective) midwives answered the items on the assessed relevance of midwifery competencies in academic education (59 items); 3 items were added (referring to evidence-based practice and digital literacy). Construct validity was tested using exploratory factor analysis. Item and reliability analysis as well as unpaired t-tests were performed. RESULTS: Considering insufficient item-construct associations (20 items), a single factorial solution best fits the data (eigenvalue: 18.36; explained variance: 29.60%). Internal reliability was demonstrated to be very good with Cronbach's α=0.954. The assessed relevance of academic midwifery competencies from academic and non-academic midwives did not differ significantly from each other for students and trainee midwives (t=0.18; df=6.66; p=0.86), and for for midwives educated at vocational school and university (t= -0.035; df=106; p=0.97). CONCLUSIONS: The adapted assessment tool can be used with minor modifications to reliably and validly measure the assessed relevance of academic competence from the midwives' perspective. Combined with data on the assessments of medical practitioners and laypersons, the assessment provides a substantial data basis for the development of a competence profile for academic midwifery education in Germany.

13.
Analyst ; 136(8): 1722-7, 2011 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-21369598

RESUMO

This article describes the synthesis and characterisation of fluorescent composite nanoparticles consisting of a silica core and a dextran shell. The silica core contains a rhodamine-based reference dye, which allows ratiometric measurements and the dextran shell is labelled with the Ca(2+)-sensitive dye Fluo-4. The nanoparticles have an average hydrodynamic diameter of 95 nm, good colloidal stability and show a 2.9-fold increase in fluorescence intensity upon binding to Ca(2+) ions. The apparent dissociation constant of K'(d) ≈ 520 nM is well suited for measurements in the physiological range.


Assuntos
Cálcio/análise , Dextranos/química , Nanopartículas/química , Dióxido de Silício/química , Espectrometria de Fluorescência/métodos , Compostos de Anilina/química , Concentração de Íons de Hidrogênio , Rodaminas/química , Xantenos/química
14.
Z Evid Fortbild Qual Gesundhwes ; 166: 8-17, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474989

RESUMO

OBJECTIVE: Development and psychometric evaluation of a multidimensional model and assessment scales measuring core aspects of the quality of woman-centred midwifery care processes in Germany. DESIGN & PARTICIPANTS: 201 women, who received midwifery care during their pregnancy in 2018, were enrolled 6 to 18 months after birth. Data were assessed in a retrospective cross-sectional survey in Germany. MEASUREMENTS: Established scales that are used in health care were adapted to the context of woman-centred midwifery care: Shared Decision-Making (SDM-Q-9-M), Empathy (CARE-M), Internal Team Participation (TEAM-M) and Professional Competence (PC-M). Confirmatory factor analyses were adapted to prove (a) the homogeneity of the single scales and (b) the multidimensional structure of the entire item pool. FINDINGS: Appropriate to good model fit was confirmed for both the single assessments (CFI ≥ .96; SRMR ≤ .032) and the multidimensional model (CFI=.96; SRMR=.049). Minor model modifications reflecting local item dependencies had to be considered for the scales SDM-Q-9-M, TEAM-M, and PC-M. For the CARE-M scale, Participatory Communication proved to be a separate, second structural component. CONCLUSIONS: Shared Decision-Making, Empathy, Internal Team Participation, and Professional Competence constitute core components of woman-centred midwifery care processes. A multi-dimensional assessment is now available measuring women's experiences with midwifery care. The assessment provides an essential component to master the complex challenge of measuring the quality of midwifery care inside and outside the hospital by means of a standardised and validated assessment.


Assuntos
Tocologia , Estudos Transversais , Feminino , Alemanha , Humanos , Mães , Gravidez , Estudos Retrospectivos
15.
Chemistry ; 16(34): 10290-9, 2010 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-20665579

RESUMO

Advances in nanoparticle technology have recently offered new tools to the bioanalytical field of research. In particular, new nanoparticle-based sensors have appeared able to give quantitative information about different species (ions, metabolites, biomolecules) in biosamples through ratiometric measurements. This article describes the methodologies developed so far in the design of such nanosensors. In particular, the different approaches to immobilize fluorescent chemosensor dyes to nanoparticles are presented. Concept designs of ratiometric nanosensors in terms of composition and architecture are also described and illustrated with examples taken from the literature.


Assuntos
Corantes/química , Corantes Fluorescentes/química , Nanopartículas/química , Técnicas Biossensoriais/métodos , Nanotecnologia/métodos , Espectrometria de Fluorescência
16.
Org Biomol Chem ; 7(9): 1884-9, 2009 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-19590784

RESUMO

The comprehensive characterization of novel dextran nanoparticles with regard to their suitability as pH-sensors for analytical applications (e.g. in physiology) is described. The nanoparticles are labeled with both a pH-indicator dye (fluorescein isothiocyanate, FITC) and a reference dye (sulforhodamine B acid chloride) as an internal standard. The fluorescence intensity of FITC increases with increasing pH, whereas the signal of the reference dye remains constant. Plotting the ratio of both signals against the pH gives a pK(a) of 6.45, which is appropriate for most of the measurement purposes. Furthermore, the influence of temperature, ionic strength and oxidizing substances on the performance of the fluorophores inside the dextran nanoparticles is examined. These results are compared to the dissolved dyes in order to evaluate if the dextran matrix affects the fluorescence properties of the sensor and the reference dye, and whether or not these nanosensors are suitable for pH-sensing in biological samples.


Assuntos
Dextranos/química , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/química , Nanopartículas/química , Rodaminas/química , Concentração de Íons de Hidrogênio , Concentração Osmolar , Oxirredução , Fotodegradação , Soluções
17.
EBioMedicine ; 41: 649-658, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819512

RESUMO

BACKGROUND: The most prevalent inherited form of generalized dystonia is caused by a mutation in torsinA (DYT1, ∆GAG) with incomplete penetrance. Rodent models with mutated torsinA do not develop dystonic symptoms, but previous ex vivo studies indicated abnormal excitation of cholinergic interneurons (ChI) and increased striatal acetylcholine. METHODS: We used in vivo optogenetics to exacerbate this endophenotype in order to determine its capacity to trigger dystonic symptoms in freely behaving mice. Tor1a+/Δgag DYT1 mice and wildtype littermates expressing channelrhodopsin2 under the Chat promotor were implanted bilaterally with optical LED cannulae and stimulated with blue light pulses of varied durations. FINDINGS: Six months old DYT1 KI mice but not wildtype controls responded with hyperactivity to blue light specifically at 25 ms pulse duration, 10 Hz frequency. Neuronal activity (c-Fos) in cholinergic interneurons was increased immediately after light stimulation and persisted only in DYT1 KI over 15 min. Substance P was increased specifically in striosome compartments in naïve DYT1 KI mice compared to wildtype. Under optogenetic stimulation substance P increased in wildtype to match levels in Dyt1 KI, and acetylcholinesterase was elevated in the striatum of stimulated DYT1 KI. No signs of dystonic movements were observed under stimulation of up to one hour in both genotypes and age groups, and the sensorimotor deficit previously observed in 6 months old DYT1 KI mice persisted under stimulation. INTERPRETATION: Overall this supports an endophenotype of dysregulated cholinergic activity in DYT1 dystonia, but depolarizing cholinergic interneurons was not sufficient to induce overt dystonia in DYT1 KI mice.


Assuntos
Neurônios Colinérgicos/metabolismo , Chaperonas Moleculares/genética , Optogenética , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos da radiação , Channelrhodopsins/metabolismo , Endofenótipos , Feminino , Técnicas de Introdução de Genes , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Substância P/genética , Substância P/metabolismo
18.
Exp Gerontol ; 43(7): 645-652, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18439778

RESUMO

It has been suggested that deletions of mitochondrial DNA (mtDNA) are important players with regard to the ageing process. Since the early 1990s, the 4977 bp deletion has been studied in various tissues, especially in postmitotic tissues with high energy demand. Unfortunately, some of these studies included less than 10 subjects, so the aim of our study was to quantify reliably the deletion amount in nine different regions of human brain, heart and skeletal muscle in a cohort of 92 individuals. The basal ganglia contain the highest deletion amounts with values up to 2.93% and differences in deletion levels between early adolescence and older ages were up to three orders of magnitude. Values in frontal lobe were on average an order of magnitude lower, but lowest in cerebellar tissue where the amount was on average only 5 x 10(-3) of the basal ganglia. The deletion started to accumulate in iliopsoas muscle early in the fourth decade of life with values between 0.00019% and 0.0035% and was highest in a 102-year-old woman with 0.14%. In comparison to skeletal muscle, the overall abundance in heart muscle of the left ventricle was only one-third. The best linear logarithmic correlation between amount of the deletion and age was found in substantia nigra with r=0.87 (p<0.0005) followed by anterior wall of the left ventricle (r=0.82; p<0.0005). With regard to mitochondrial DNA damage, we propose to use the 4977 bp deletion as an ideal biomarker to discriminate between physiological ageing and accelerated ageing. The biological meaning of mitochondrial deletions in the process of ageing is under discussion, but there is experimental evidence that large-scale deletions impair the oxidative phosphorylation in single cells and sensitize these cells to undergo apoptosis.


Assuntos
Química Encefálica , DNA Mitocondrial/genética , Músculo Esquelético/química , Miocárdio/química , Deleção de Sequência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Criança , Pré-Escolar , Marcadores Genéticos , Humanos , Lactente , Pessoa de Meia-Idade , Mitocôndrias Cardíacas/genética , Mitocôndrias Musculares/genética , Reação em Cadeia da Polimerase/métodos
19.
Child Abuse Negl ; 76: 225-236, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29149683

RESUMO

Prevalence of Internet use among adolescents is high, but little is known about the online sexual activities of German adolescents. This study aimed to describe the 12-month prevalence of German adolescents' online sexual experiences with a focus on Online Sexual Solicitation (OSS, subjectively negative online sexual experiences with a peer or any sexual online experience, positive or negative, with an adult). A sample of male and female adolescents aged 14-17 (N=2238) was recruited using online survey panel. The sample was representative for gender and education. Subjects completed an online survey reporting their online sexual activities (i.e., sexual conversation, exchanging pictures, and cybersex) with peers (14-17y.) and/or adults (≥18y.). Findings illustrated that 51.3% (n=1148) of adolescents had experienced online sexual activity, which mostly involved peers (n=969; 84.4%). In contrast, 23.2% (n=519) of the adolescents experienced OSS with 2.6% (n=57) reporting subjectively negative online sexual interactions with peers and 22.2% (n=490) reporting online sexual interactions with adults, of which 10.4% (n=51) were perceived as negative. The findings suggest that adolescents frequently engage in sexual interactions on the Internet with only a relatively small number perceiving such contacts as exploitative. In addition, females and adolescents with incomplete family situation, foreign nationality, higher education, homo- or bisexual orientation, and those without perceived social support reported OSS significantly more often.


Assuntos
Internet/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Adolescente , Bissexualidade/psicologia , Comunicação , Feminino , Heterossexualidade/psicologia , Humanos , Relações Interpessoais , Masculino , Grupo Associado , Fatores Sexuais , Comportamento Sexual/psicologia , Inquéritos e Questionários
20.
Obes Res Clin Pract ; 11(1): 127-129, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27887923

RESUMO

Obesity has been related to deficient mental rotation performance. We assessed object-based and egocentric MR tasks in 19 obese and 19 normal-weight participants. Results showed slower response times of obese adolescents only for high angular disparities. This finding might emerge because of impairments in working memory, motor skills or perspective taking processes in obese youth.


Assuntos
Processos Mentais , Obesidade/psicologia , Tempo de Reação , Rotação , Processamento Espacial , Adolescente , Feminino , Humanos , Masculino
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