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1.
J Physiol ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850551

RESUMO

Circadian rhythms, governed by the dominant central clock, in addition to various peripheral clocks, regulate almost all biological processes, including sleep-wake cycles, hormone secretion and metabolism. In certain contexts, the regulation and function of the peripheral oscillations can be decoupled from the central clock. However, the specific mechanisms underlying muscle-intrinsic clock-dependent modulation of muscle function and metabolism remain unclear. We investigated the outcome of perturbations of the primary and secondary feedback loops of the molecular clock in skeletal muscle by specific gene ablation of Period circadian regulator 2 (Per2) and RAR-related orphan receptor alpha (Rorα), respectively. In both models, a dampening of core clock gene oscillation was observed, while the phase was preserved. Moreover, both loops seem to be involved in the homeostasis of amine groups. Highly divergent outcomes were seen for overall muscle gene expression, primarily affecting circadian rhythmicity in the PER2 knockouts and non-oscillating genes in the RORα knockouts, leading to distinct outcomes in terms of metabolome and phenotype. These results highlight the entanglement of the molecular clock and muscle plasticity and allude to specific functions of different clock components, i.e. the primary and secondary feedback loops, in this context. The reciprocal interaction between muscle contractility and circadian clocks might therefore be instrumental to determining a finely tuned adaptation of muscle tissue to perturbations in health and disease. KEY POINTS: Specific perturbations of the primary and secondary feedback loop of the molecular clock result in specific outcomes on muscle metabolism and function. Ablation of Per2 (primary loop) or Rorα (secondary loop) blunts the amplitude of core clock genes, in absence of a shift in phase. Perturbation of the primary feedback loop by deletion of PER2 primarily affects muscle gene oscillation. Knockout of RORα and the ensuing modulation of the secondary loop results in the aberrant expression of a large number of non-clock genes and proteins. The deletion of PER2 and RORα affects muscle metabolism and contractile function in a circadian manner, highlighting the central role of the molecular clock in modulating muscle plasticity.

2.
PLoS Genet ; 17(7): e1009625, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34237069

RESUMO

Light at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle. Here we provide evidence that light at zeitgeber time (ZT) 22 affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors. We show that complete deletion of Per1 in mice led to depressive-like behavior and loss of the beneficial effects of light on this behavior. In contrast, specific deletion of Per1 in the region of the LHb did not affect mood-related behavior, but suppressed the beneficial effects of light. RNA sequence analysis in the mesolimbic dopaminergic system revealed profound changes of gene expression after a light pulse at ZT22. In the nucleus accumbens (NAc), sensory perception of smell and G-protein coupled receptor signaling were affected the most. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene expression in the brain. Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on mood-related behavior and signaling mechanisms in the mesolimbic dopaminergic system.


Assuntos
Comportamento Animal/fisiologia , Habenula/fisiologia , Proteínas Circadianas Period/genética , Afeto/fisiologia , Animais , Depressão/genética , Feminino , Regulação da Expressão Gênica , Luz , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Circadianas Period/metabolismo
3.
BMC Musculoskelet Disord ; 24(1): 146, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823560

RESUMO

BACKGROUND: Although apps are becoming increasingly relevant in healthcare, there is limited knowledge about how healthcare professionals perceive "quality" in this context and how quality principles that can aid them in assessing health-related apps may be prioritised. The objective was to investigate physicians' views of predefined (general) quality principles for health apps and to determine whether a ranking algorithm applied to the acquired data can provide stable results against various demographic influences and may thus be appropriate for prioritisation. METHODS: Participants of an online survey of members of two German professional orthopaedics associations conducted between 02/12/2019 and 02/01/2020 were asked about their perception of a set of quality principles for health apps (i.e., "practicality," "risk adequacy," "ethical soundness," "legal conformity," "content validity," "technical adequacy," "usability," "resource efficiency," and "transparency"). Structured as a Kano survey, for each principle, there were questions about its perceived relevance and opinions regarding the presence or absence of corresponding characteristics. The available data were evaluated descriptively, and a newly developed method for prioritisation of the principles was applied overall and to different demographic strata (for validation). RESULTS: Three hundred eighty-two datasets from 9503 participants were evaluated. Legal conformity, content validity, and risk adequacy filled ranks one to three, followed by practicability, ethical soundness, and usability (ranks 4 to 6). Technical adequacy, transparency, and resource efficiency ranked last (ranks 7 to 9). The ranking based on the proposed method was relatively stable, irrespective of demographic factors. The principles were seen as essential, with one exception ("resource efficiency"). Only those with little to no interest in digitisation (22/382, 5.8%) rated the nine principles indifferently. CONCLUSIONS: The specified quality principles and their prioritisation can lay a foundation for future assessments of apps in the medical field. Professional societies build upon this to highlight opportunities for digital transformations in medicine and encourage their members to participate.


Assuntos
Aplicativos Móveis , Ortopedia , Cirurgiões , Humanos , Nigéria , Demografia
4.
Internist (Berl) ; 63(3): 274-280, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35147711

RESUMO

Mobile health (mHealth) for the detection of atrial fibrillation is an innovative domestic monitoring of the heart rhythm. The use of mHealth in the context of atrial fibrillation increases the availability of diagnostic technologies and facilitates the integration into telemedical treatment concepts as well as the active participation of patients in the treatment process. The detection of atrial fibrillation with mHealth applications is usually based on electrocardiography (ECG) or by detection of the pulse wave using photoplethysmography (PPG). Some applications require additional sensors, others make use of sensors integrated into smartphones or smartwatches. A high diagnostic accuracy for the detection of atrial fibrillation has been shown for most mHealth applications regardless of the underlying technology (analytical validation); however, the evidence on positive care effects and improvement of medical endpoints (clinical validation) is so far scarce. Screening of symptomatic or asymptomatic patients and the follow-up care after antiarrhythmic measures are possibilities for the integration into the reality of care. The preventive detection of atrial fibrillation is an attractive field of application for mHealth with great potential for the future. Nevertheless, at present mHealth is only integrated to a limited extent into the reality of patient care. Adequate reimbursement and medical remuneration as well as opportunities to derive information and qualification are prerequisites in order to be able to guarantee a comprehensive implementation in the future. The Digital Health Care Act passed in 2019, regulates the reimbursement of digital healthcare applications but issues of primary preventive applications have not yet been included.


Assuntos
Fibrilação Atrial , Aplicativos Móveis , Telemedicina , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Eletrocardiografia , Humanos , Fotopletismografia
5.
Circulation ; 140(13): 1100-1114, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31401849

RESUMO

BACKGROUND: The incidence of acute cardiovascular complications is highly time-of-day dependent. However, the mechanisms driving rhythmicity of ischemic vascular events are unknown. Although enhanced numbers of leukocytes have been linked to an increased risk of cardiovascular complications, the role that rhythmic leukocyte adhesion plays in different vascular beds has not been studied. METHODS: We evaluated leukocyte recruitment in vivo by using real-time multichannel fluorescence intravital microscopy of a tumor necrosis factor-α-induced acute inflammation model in both murine arterial and venous macrovasculature and microvasculature. These approaches were complemented with genetic, surgical, and pharmacological ablation of sympathetic nerves or adrenergic receptors to assess their relevance for rhythmic leukocyte adhesion. In addition, we genetically targeted the key circadian clock gene Bmal1 (also known as Arntl) in a lineage-specific manner to dissect the importance of oscillations in leukocytes and components of the vessel wall in this process. RESULTS: In vivo quantitative imaging analyses of acute inflammation revealed a 24-hour rhythm in leukocyte recruitment to arteries and veins of the mouse macrovasculature and microvasculature. Unexpectedly, although in arteries leukocyte adhesion was highest in the morning, it peaked at night in veins. This phase shift was governed by a rhythmic microenvironment and a vessel type-specific oscillatory pattern in the expression of promigratory molecules. Differences in cell adhesion molecules and leukocyte adhesion were ablated when disrupting sympathetic nerves, demonstrating their critical role in this process and the importance of ß2-adrenergic receptor signaling. Loss of the core clock gene Bmal1 in leukocytes, endothelial cells, or arterial mural cells affected the oscillations in a vessel type-specific manner. Rhythmicity in the intravascular reactivity of adherent leukocytes resulted in increased interactions with platelets in the morning in arteries and in veins at night with a higher predisposition to acute thrombosis at different times as a consequence. CONCLUSIONS: Together, our findings point to an important and previously unrecognized role of artery-associated sympathetic innervation in governing rhythmicity in vascular inflammation in both arteries and veins and its potential implications in the occurrence of time-of-day-dependent vessel type-specific thrombotic events.


Assuntos
Artérias/imunologia , Endotélio Vascular/metabolismo , Inflamação/imunologia , Leucócitos/fisiologia , Trombose/fisiopatologia , Veias/imunologia , Animais , Artérias/inervação , Artérias/patologia , Adesão Celular , Células Cultivadas , Relógios Circadianos , Endotélio Vascular/patologia , Regulação da Expressão Gênica , Humanos , Microscopia Intravital , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Periodicidade , Receptores Adrenérgicos beta 2/metabolismo , Sistema Nervoso Simpático , Fator de Necrose Tumoral alfa/metabolismo , Veias/inervação , Veias/patologia
6.
Curr Sports Med Rep ; 19(4): 157-163, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282462

RESUMO

Digital transformation is becoming increasingly common in modern life and sports medicine, like many other medical disciplines, it is strongly influenced and impacted by this rapidly changing field. This review aims to give a brief overview of the potential that digital technologies can have for health care providers and patients in the clinical practice of sports medicine. We will focus on mobile applications, wearables, smart devices, intelligent machines, telemedicine, artificial intelligence, big data, system interoperability, virtual reality, augmented reality, exergaming, or social networks. While some technologies are already used in current medical practice, others still have undiscovered potential. Due to the diversity and ever changing nature of this field, we will briefly review multiple areas in an attempt to give readers some general exposure to the landscape instead of a thorough, deep review of one topic. Further research will be necessary to show how digitalization applications could best be used for patient treatments.


Assuntos
Medicina Esportiva , Inteligência Artificial , Big Data , Humanos , Aplicativos Móveis , Telemedicina , Dispositivos Eletrônicos Vestíveis
7.
Laryngorhinootologie ; 98(S 01): S253-S289, 2019 Mar.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-31096301

RESUMO

The implementation of mobile information and communication technology in the field of health services, e. g. in the form of apps, is becoming increasingly important. Unfortunately, the necessary quality criteria are often mising. Thus, it seems important, that in addition to an app controlling authority highly qualified health care professionals participate in the development of these applications. For reasons of liability, however, the physician must exercise great caution in the selection and recommendation of medical apps, especially considering, that only a few apps are certified as medical devices. There are a large number of medical apps on the market, with only a small proportion being assigned to the field of otorhinolaryngology. The areas of audiology, sleep medicine and allergology are most frequently represented. Althouhgh there is increasing scientific work on this topic in the field of otorhinolaryngology, there is a lack of scientific evidence of contents and results, as is generally the case of medical apps. However, there are other possibilities for users to rate medical apps regarding defined qualitiy criteria such as functionality, scientific integrity, but also data privacy. None of the apps assessed by such a evaluation tool met all the required quality criteria, but the applied instrument helped to better assess the application. However, it was possible to consider the quality criteria in the developmental process of an medical app for the field of otorhinolaryngoglogy. In summary, the present work provide a comprehensive insight into the topic "Apps in Otorhinolaryngology" with the aim to use these modern aids in a beneficial way.


Assuntos
Aplicativos Móveis , Otolaringologia
8.
J Cell Sci ; 129(21): 4143-4154, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27686098

RESUMO

REV-ERBα (encoded by Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, encoded by Nr3c1) influences similar processes, but is not part of the circadian clock, although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes, we studied the interplay between these two nuclear receptors. We found that REV-ERBα binds to the C-terminal portion and GR to the N-terminal portion of HSP90α and HSP90ß, a chaperone responsible for the activation of proteins to ensure survival of a cell. The presence of REV-ERBα influences the stability and nuclear localization of GR by an unknown mechanism, thereby affecting expression of GR target genes, such as IκBα (Nfkbia) and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence the transcriptional potential of each other. This indicates that the transcriptional landscape is strongly dependent on dynamic processes at the protein level.


Assuntos
Núcleo Celular/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Células Cultivadas , Ritmo Circadiano , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP90/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Ligação Proteica , Estabilidade Proteica , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genética , Frações Subcelulares/metabolismo , Fatores de Tempo
9.
Nature ; 483(7387): 96-9, 2012 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-22367544

RESUMO

Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada's syndrome) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, krüppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.


Assuntos
Arritmias Cardíacas/fisiopatologia , Ritmo Circadiano/fisiologia , Sistema de Condução Cardíaco/fisiologia , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/genética , Células Cultivadas , Ritmo Circadiano/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Regulação da Expressão Gênica , Frequência Cardíaca/fisiologia , Ventrículos do Coração/citologia , Fatores de Transcrição Kruppel-Like , Proteínas Interatuantes com Canais de Kv/biossíntese , Proteínas Interatuantes com Canais de Kv/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Musculares/citologia , Regiões Promotoras Genéticas/genética , Ratos , Fatores de Tempo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Genes Dev ; 24(4): 345-57, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20159955

RESUMO

Mammalian circadian clocks provide a temporal framework to synchronize biological functions. To obtain robust rhythms with a periodicity of about a day, these clocks use molecular oscillators consisting of two interlocked feedback loops. The core loop generates rhythms by transcriptional repression via the Period (PER) and Cryptochrome (CRY) proteins, whereas the stabilizing loop establishes roughly antiphasic rhythms via nuclear receptors. Nuclear receptors also govern many pathways that affect metabolism and physiology. Here we show that the core loop component PER2 can coordinate circadian output with the circadian oscillator. PER2 interacts with nuclear receptors including PPARalpha and REV-ERBalpha and serves as a coregulator of nuclear receptor-mediated transcription. Consequently, PER2 is rhythmically bound at the promoters of nuclear receptor target genes in vivo. In this way, the circadian oscillator can modulate the expression of nuclear receptor target genes like Bmal1, Hnf1alpha, and Glucose-6-phosphatase. The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks.


Assuntos
Ritmo Circadiano/fisiologia , Regulação da Expressão Gênica , Proteínas Circadianas Period/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição ARNTL/metabolismo , Motivos de Aminoácidos , Animais , Ritmo Circadiano/genética , Glucose/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Knockout , Células NIH 3T3 , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , PPAR alfa/metabolismo , Proteínas Circadianas Period/genética , Regiões Promotoras Genéticas , Ligação Proteica
11.
Artigo em Alemão | MEDLINE | ID: mdl-29368121

RESUMO

For a number of reasons, achieving reimbursability for digital health products has so far proven difficult. Demonstrating the benefits of the technology is the main hurdle in this context. The generally accepted evaluation processes, especially parallel group comparisons in randomized controlled trials (RCTs) for (clinical) benefit assessment, are primarily intended to deal with questions of (added) medical benefit. In contrast to drugs or classical medical devices, users of digital health solutions often profit from gaining autonomy, increased awareness and mindfulness, better transparency in the provision of care, and improved comfort, although there are also digital solutions with an interventional character targeting clinical outcomes (e. g. for indications such as anorexia, depression). Commonly accepted methods for evaluating (clinical) benefits primarily rely on medical outcomes, such as morbidity and mortality, but do not adequately consider additional benefits unique to digital health. The challenge is therefore to develop evaluation designs that respect the particularities of digital health without reducing the validity of the evaluations (especially with respect to safety). There is an increasing need for concepts that include both continuous feedback loops for adapting and improving an application while at the same time generate sufficient evidence for complex benefit assessments. This approach may help improve risk benefit ratio assessments of digital health when it comes to implementing digital innovations in healthcare.


Assuntos
Programas Nacionais de Saúde/tendências , Mecanismo de Reembolso/tendências , Telemedicina/tendências , Análise Custo-Benefício/tendências , Previsões , Alemanha , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências
12.
Nature ; 480(7376): 209-14, 2011 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-22080954

RESUMO

Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Folículo Piloso/citologia , Células-Tronco/citologia , Fatores de Transcrição ARNTL/deficiência , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Adesão Celular/genética , Ciclo Celular/genética , Células Cultivadas , Senescência Celular , Relógios Circadianos/genética , Ritmo Circadiano/genética , Sinais (Psicologia) , Feminino , Regulação da Expressão Gênica/genética , Homeostase/genética , Homeostase/fisiologia , Masculino , Camundongos , Camundongos Knockout , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Nicho de Células-Tronco , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/genética , Via de Sinalização Wnt/genética
13.
Addict Biol ; 22(2): 411-422, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26632340

RESUMO

The drive to eat is regulated by two compensatory brain pathways termed as homeostatic and hedonic. Hypothalamic orexinergic (ORX) neurons regulate metabolism, feeding and reward, thus controlling physiological and hedonic appetite. Circadian regulation of feeding, metabolism and rhythmic activity of ORX cells are driven by the brain suprachiasmatic clock. How the circadian clock impacts on ORX signalling and feeding-reward rhythms is, however, unknown. Here we used mice lacking the nuclear receptor REV-ERBα, a transcription repressor and a key component of the molecular clockwork, to study food-reward behaviour. Rev-Erbα mutant mice showed highly motivated behaviours to obtain palatable food, an increase in the intake and preference for tasty diets, and in the expression of the ORX protein in the hypothalamus. Palatable food intake was inhibited in animals treated with the ORX1R antagonist. Analyzing the Orx promoter, we found Retinoic acid-related Orphan receptor Response Element binding sites for Rev-Erbα. Furthermore, Rev-Erbα dampened the activation of Orx in vitro and in vivo. Our data provide evidence for a possible repressive role of Rev-Erbα in the regulation of ORX signalling, highlighting an implication of the circadian clockwork in modulating food-reward behaviours with an important impact for the central regulation of overeating.


Assuntos
Ingestão de Alimentos/genética , Comportamento Alimentar/fisiologia , Hipotálamo/metabolismo , Neurônios/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Orexinas/metabolismo , Animais , Ritmo Circadiano , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Antagonistas dos Receptores de Orexina/farmacologia , Receptores de Orexina/metabolismo , Regiões Promotoras Genéticas , Transdução de Sinais
14.
Nucleic Acids Res ; 43(4): 2126-37, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25662220

RESUMO

The efficiency of Nucleotide Excision Repair (NER)process is crucial for maintaining genomic integrity because in many organisms, including humans, it represents the only system able to repair a wide range of DNA damage. The aim of the work was to investigate whether the efficiency of the repair of photoproducts induced by UV-light is affected by the circadian phase at which irradiation occurred. NER activity has been analyzed in human quiescent fibroblasts (in the absence of the cell cycle effect), in which circadian rhythmicity has been synchronized with a pulse of dexamethasone. Our results demonstrate that both DNA damage induction and repair efficiency are strictly dependent on the phase of the circadian rhythm at which the cells are UV-exposed. Furthermore, the differences observed between fibroblasts irradiated at different circadian times (CTs) are abolished when the clock is obliterated. In addition, we observe that chromatin structure is regulated by circadian rhythmicity. Maximal chromatin relaxation occurred at the same CT when photoproduct formation and removal were highest. Our data suggest that the circadian clock regulates both the DNA sensitivity to UV damage and the efficiency of NER by controlling chromatin condensation mainly through histone acetylation.


Assuntos
Relógios Circadianos/genética , Reparo do DNA , Linhagem Celular , Células Cultivadas , Cromatina/metabolismo , Dexametasona/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Dímeros de Pirimidina/metabolismo , Raios Ultravioleta , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo
15.
Proc Natl Acad Sci U S A ; 110(5): 1592-9, 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23267082

RESUMO

Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for wound healing in mice. Specifically, although fibroblasts from NONO-deficient mice showed approximately normal circadian cycles, they displayed elevated cell doubling and lower cellular senescence. At a molecular level, NONO bound to the p16-Ink4A cell cycle checkpoint gene and potentiated its circadian activation in a PER protein-dependent fashion. Loss of either NONO or PER abolished this activation and circadian expression of p16-Ink4A and eliminated circadian cell cycle gating. In vivo, lack of NONO resulted in defective wound repair. Because wound healing defects were also seen in multiple circadian clock-deficient mouse lines, our results therefore suggest that coupling of the cell cycle to the circadian clock via NONO may be useful to segregate in temporal fashion cell proliferation from tissue organization.


Assuntos
Ciclo Celular/fisiologia , Relógios Circadianos/fisiologia , Proteínas de Ligação a DNA/metabolismo , Proteínas Circadianas Period/metabolismo , Animais , Western Blotting , Ciclo Celular/genética , Proliferação de Células , Células Cultivadas , Senescência Celular/genética , Senescência Celular/fisiologia , Relógios Circadianos/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteínas de Ligação a DNA/genética , Derme/metabolismo , Derme/patologia , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Proteínas Circadianas Period/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica , Interferência de RNA , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores/genética , Transativadores/metabolismo , Cicatrização/genética , Cicatrização/fisiologia
16.
J Med Internet Res ; 16(2): e53, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24521935

RESUMO

BACKGROUND: Google Glass is a promising premarket device that includes an optical head-mounted display. Several proof of concept reports exist, but there is little scientific evidence regarding its use in a medical setting. OBJECTIVE: The objective of this study was to empirically determine the feasibility of deploying Glass in a forensics setting. METHODS: Glass was used in combination with a self-developed app that allowed for hands-free operation during autopsy and postmortem examinations of 4 decedents performed by 2 physicians. A digital single-lens reflex (DSLR) camera was used for image comparison. In addition, 6 forensic examiners (3 male, 3 female; age range 23-48 years, age mean 32.8 years, SD 9.6; mean work experience 6.2 years, SD 8.5) were asked to evaluate 159 images for image quality on a 5-point Likert scale, specifically color discrimination, brightness, sharpness, and their satisfaction with the acquired region of interest. Statistical evaluations were performed to determine how Glass compares with conventionally acquired digital images. RESULTS: All images received good (median 4) and very good ratings (median 5) for all 4 categories. Autopsy images taken by Glass (n=32) received significantly lower ratings than those acquired by DSLR camera (n=17) (region of interest: z=-5.154, P<.001; sharpness: z=-7.898, P<.001; color: z=-4.407, P<.001, brightness: z=-3.187, P=.001). For 110 images of postmortem examinations (Glass: n=54, DSLR camera: n=56), ratings for region of interest (z=-8.390, P<.001) and brightness (z=-540, P=.007) were significantly lower. For interrater reliability, intraclass correlation (ICC) values were good for autopsy (ICC=.723, 95% CI .667-.771, P<.001) and postmortem examination (ICC=.758, 95% CI .727-.787, P<.001). Postmortem examinations performed using Glass took 42.6 seconds longer than those done with the DSLR camera (z=-2.100, P=.04 using Wilcoxon signed rank test). The battery charge of Glass quickly decreased; an average 5.5% (SD 1.85) of its battery capacity was spent per postmortem examination (0.81% per minute or 0.79% per picture). CONCLUSIONS: Glass was efficient for acquiring images for documentation in forensic medicine, but the image quality was inferior compared to a DSLR camera. Images taken with Glass received significantly lower ratings for all 4 categories in an autopsy setting and for region of interest and brightness in postmortem examination. The effort necessary for achieving the objectives was higher when using the device compared to the DSLR camera thus extending the postmortem examination duration. Its relative high power consumption and low battery capacity is also a disadvantage. At the current stage of development, Glass may be an adequate tool for education. For deployment in clinical care, issues such as hygiene, data protection, and privacy need to be addressed and are currently limiting chances for professional use.


Assuntos
Autopsia , Medicina Legal/instrumentação , Prontuários Médicos , Aplicativos Móveis , Fotografação/instrumentação , Adulto , Documentação , Estudos de Viabilidade , Feminino , Medicina Legal/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Privacidade
17.
Annu Rev Physiol ; 72: 517-49, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20148687

RESUMO

Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.


Assuntos
Relógios Biológicos/fisiologia , Sistema Nervoso Central/fisiologia , Ritmo Circadiano/fisiologia , Sistema Nervoso Periférico/fisiologia , Animais , Relógios Biológicos/efeitos dos fármacos , Encéfalo/fisiologia , Sistema Nervoso Central/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Alimentos , Humanos , Sistema Nervoso Periférico/efeitos dos fármacos , Reforço Psicológico , Recompensa , Núcleo Supraquiasmático/fisiologia
18.
Arch Orthop Trauma Surg ; 134(12): 1683-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25367440

RESUMO

PURPOSE: Cranial migration of shoulder hemiarthroplasties due to rotator cuff insufficiency typically requires conversion into a reverse total shoulder arthroplasty. This study was conducted to analyze differences between the height and offset of six implants designed to enable conversion of a hemiarthroplasty into a reverse system. METHODS: Anteroposterior radiographs of 40 shoulders were taken. An image analyzing software was used to simulate the implantation of the hemiprostheses. Then the implant was dissembled, leaving on the stem within the humeral shaft. Finally, the implantation of a reverse system was simulated using the stem in the same position. Values are reported as ∆-height and ∆-offset ± standard deviation. Significance was assumed for P < 0.05. RESULTS: The least decrease in height was determined for Implantcast with 11.6 ± 3.3 mm, followed by DePuy (16 ± 5.7 mm) and the greatest for Tornier with 33 ± 5.3 mm. No significant differences were found among Exactech, Mathys and Zimmer. The largest offset-deviation was calculated for DePuy (-21.7 ± 3.7 mm) and the smallest for Implantcast (-3.3 ± 2.8 mm) and Tornier (1.5 ± 5.7 mm). CONCLUSIONS: Due to the modular stem, the system of Implantcast can be converted in a reverse system with the least changes in height and offset. For the other manufacturers it does not seem possible to convert a hemiprosthesis to a reversed prosthesis without accepting additional tension of the deltoid muscle. Further experimental studies have to analyze the changes in deltoid abduction moments after conversion of a hemi- into a reversed prosthesis.


Assuntos
Artroplastia de Substituição/métodos , Hemiartroplastia , Prótese Articular , Desenho de Prótese , Articulação do Ombro/cirurgia , Adulto , Idoso , Músculo Deltoide , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Radiografia , Amplitude de Movimento Articular/fisiologia , Reoperação , Articulação do Ombro/diagnóstico por imagem
19.
Bioengineering (Basel) ; 11(6)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38927832

RESUMO

In recent decades, much work has been implemented in heart rate (HR) analysis using electrocardiographic (ECG) signals. We propose that algorithms developed to calculate HR based on detected R-peaks using ECG can be applied to seismocardiographic (SCG) signals, as they utilize common knowledge regarding heart rhythm and its underlying physiology. We implemented the experimental framework with methods developed for ECG signal processing and peak detection to be applied and evaluated on SCGs. Furthermore, we assessed and chose the best from all combinations of 15 peak detection and 6 preprocessing methods from the literature on the CEBS dataset available on Physionet. We then collected experimental data in the lab experiment to measure the applicability of the best-selected technique to the real-world data; the abovementioned method showed high precision for signals recorded during sitting rest (HR difference between SCG and ECG: 0.12 ± 0.35 bpm) and a moderate precision for signals recorded with interfering physical activity-reading out a book loud (HR difference between SCG and ECG: 6.45 ± 3.01 bpm) when compared to the results derived from the state-of-the-art photoplethysmographic (PPG) methods described in the literature. The study shows that computationally simple preprocessing and peak detection techniques initially developed for ECG could be utilized as the basis for HR detection on SCG, although they can be further improved.

20.
Stud Health Technol Inform ; 316: 320-324, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39176737

RESUMO

Germany's Digital Healthcare Act allows doctors to prescribe digital health applications (DiGAs) for reimbursement. DiGAs must demonstrate safety, data security, and a "positive impact on care" to be listed in the official directory. Previously, data for permanently listed DiGAs was analyzed. The work presented here evaluates additional data fields for the currently listed DiGAs (both provisionally and permanently included) and aims to assess the completeness, details and consistency of the information. The data for this analysis was scraped from the directory and evaluated to identify potential shortcomings in the information provided.


Assuntos
Telemedicina , Alemanha , Segurança Computacional , Aplicações da Informática Médica , Humanos
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