Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
BMC Health Serv Res ; 24(1): 407, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561774

RESUMO

BACKGROUND: As the COVID-19 pandemic swept across the globe at the beginning of 2020, healthcare systems were forced to rapidly adapt and expand to meet the sudden surge in demand for intensive care services. This study is the first systematic analysis of the strategies employed by German hospitals to recruit personnel and expand bed capacities during the first wave of the pandemic, and to evaluate the effectiveness of those recruitment measures. METHODS: 152 German hospitals with intensive care capacities were selected and invited to participate in an online-based retrospective survey. Factors like the geographic distribution, individual COVID burden and level of care were considered for inclusion in the sample. The data were analyzed descriptively. RESULTS: A total of 41 hospitals participated in the survey. The additional demand for intensive care beds was met primarily by activating intensive care beds that were previously considered as non-operational in existing intensive care units (81% of respondents) and by upgrading recovery rooms (73%). The physician staffing requirements were met at approximately 75%, while the nursing staffing requirements were only met by about 45%. Staffing needs were met through reallocations/transfers (85%), staff recruitment from parental leave or retirement (49%), increased hours worked by internal staff (49%), new staff hiring (44%) and increased use of temporary staff (32%). Staff reallocations/transfers to critical care within a hospital were rated as the most effective measure. In this context, specialized personnel mostly from anesthesiology departments were appointed to intensive care medicine. CONCLUSIONS: Despite multiple recruitment efforts, the pandemic has exacerbated the nursing staff shortage. The reallocation of existing staff within hospitals was a key element in covering the staffing needs. However, additional measures and efforts are required in order to ensure that critically ill patients can be cared for without compromise. The results of this study may have important implications for healthcare providers and policymakers, offering an evidence-based foundation for responding to future public health emergencies with agility, efficiency, and success.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Retrospectivos , Unidades de Terapia Intensiva , Cuidados Críticos , Recursos Humanos , Inquéritos e Questionários
2.
J Sleep Res ; 31(5): e13550, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35060218

RESUMO

The aim of this study was to determine whether the multicomponent drug Neurexan could mitigate acute insomnia after exposure to a psychosocial stressor. We administered Neurexan orally to rats and examined stress-induced insomnia using the male rat dirty cage exchange method. The neurocircuitry and electrophysiological correlates of the model are characterised, and it represents various human insomnia conditions. Male rats were randomly assigned in a crossover design to six treatment groups and electroencephalography (EEG) electrodes attached. Three groups were exposed to a cage inhabited by another male rat for a week and the other three groups received a clean cage. Prior to cage change, rats were given either no drug, vehicle control or Neurexan. Non-rapid eye movement (NREM) sleep, REM sleep, and waking were assessed manually via EEG recordings. Group means were compared for sleep latency and for the 2 h after cage change for: time in each state, state-specific episode duration/frequency, in addition to NREM delta, gamma and REM theta EEG spectral power. Rats administered Neurexan fell asleep faster than vehicle-treated rats and spent less time awake with shorter, albeit more waking episodes and increased NREM episodes after dirty cage exposure. Neurexan-treated rats given dirty cages were not statistically different on any outcomes from Neurexan-treated rats given clean cages, thereby mitigating the stressor. In the EEG power spectra analysed, changes between treatment groups were not detected. This research confirms that Neurexan treatment has somnogenic effects and ameliorates psychological stressor-induced acute insomnia.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Animais , Estudos Cross-Over , Eletroencefalografia , Masculino , Extratos Vegetais , Ratos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/etiologia , Sono REM/fisiologia
3.
Anaesthesist ; 71(1): 21-29, 2022 01.
Artigo em Alemão | MEDLINE | ID: mdl-34283258

RESUMO

BACKGROUND: The COVID-19 pandemic posed enormous challenges to the German healthcare system and highlighted the need for strategies to recruit, train, and deploy medical personnel. Until now, no holistic concept existed to use medical students as support for professionals in intensive care units (ICU) to avoid staff shortages in medical care. METHOD: In a large-scale pilot project 265 medical students were trained for an ICU assignment. The innovative training module was accompanied by a pre-post questionnaire for self-assessment of the skills learned. 22 weeks after the training module and still during the pandemic deployment, another questionnaire was used to evaluate experiences in deployment and the efficiency of the training module with respect to preparation for ICU deployment. RESULTS: The analysis revealed significant mean differences for all COVID-19-specific variables (safety dimension) in favor of the training module (n = 168). The deployment evaluation showed that the training concept was inconsistently assessed as preparation for the work deployment for 69 of the 89 deployed students in total (53% agreement/47% disagreement). CONCLUSION: The results show a good feasibility of an innovative training concept for medical students with respect to a pandemic deployment as assistants in intensive care units. The concept is suitable for providing additional helpers in intensive care units during a pandemic; however, the inconsistent evaluation indicates that the concept can be expanded and needs to be adapted.


Assuntos
COVID-19 , Estudantes de Medicina , Humanos , Pandemias , Projetos Piloto , SARS-CoV-2
4.
Angew Chem Int Ed Engl ; 61(30): e202203950, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35644923

RESUMO

Although ylides are commonly used reagents in organic synthesis, the parent methylphosphine MePH2 only exists in its phosphine form in the condensed phase. Its ylide tautomer H3 P+ -CH2 - is considerably higher in energy. Here, we report on the formation of bis(sulfonyl)methyl-substituted phosphines of the type (RO2 S)2 C(H)-PR2, which form stable PH ylides under ambient conditions, amongst the first examples of an acyclic phosphine which only exists in its PH ylide form. Depending on the exact substitution pattern the phosphines form an equilibrium between the PH ylide and the phosphine form or exist as one of both extremes. These phosphines were found to be ideal starting systems for the facile formation of α-carbanionic phosphines. The carbanion-functionalization leads to a switch from electron-poor to highly electron-rich phosphines with strong donor abilities and high basicities. Thus, the phosphines readily react with different electrophiles exclusively at the phosphorus atom and not at the carbanionic center. Furthermore, the anionic nature of the phosphines allows the formation of zwitterionic complexes as demonstrated by the isolation of a gold(I) complex with a cationic metal center. The cationic gold center allows for catalytic activity in the hydroamination of alkyne without requiring a further activation step.

5.
Angew Chem Int Ed Engl ; 60(1): 493-498, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33006796

RESUMO

s-Block metal carbenoids are carbene synthons and applied in a myriad of organic transformations. They exhibit a strong structure-activity relationship, but this is only poorly understood due to the challenging high reactivity and sensitivity of these reagents. Here, we report on systematic VT and DOSY NMR studies, XRD analyses as well as DFT calculations on a sulfoximinoyl-substituted model system to explain the pronounced solvent dependency of the carbenoid stability. While the sodium and potassium chloride carbenoids showed high stabilities independent of the solvent, the lithium carbenoid was stable at room temperature in THF but decomposed at -10 °C in toluene. These divergent stabilities could be explained by the different structures formed in solution. In contrast to simple organolithium reagents, the monomeric THF-solvate was found to be more stable than the dimer in toluene, since the latter more readily forms direct Li/Cl interactions which facilitate decomposition via α-elimination.

6.
J Inherit Metab Dis ; 42(5): 1030-1039, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31032972

RESUMO

Murine succinic semialdehyde dehydrogenase deficiency (SSADHD) manifests with high concentrations of γ-aminobutyric acid (GABA) and γ-hydroxybutyrate (GHB) and low glutamine in the brain. To understand the pathogenic contribution of central glutamine deficiency, we exposed aldh5a1-/- (SSADHD) mice and their genetic controls (aldh5a1+/+ ) to either a 4% (w/w) glutamine-containing diet or a glutamine-free diet from conception until postnatal day 30. Endpoints included brain, liver and blood amino acids, brain GHB, ataxia scores, and open field testing. Glutamine supplementation did not improve aldh5a1-/- brain glutamine deficiency nor brain GABA and GHB. It decreased brain glutamate but did not change the ratio of excitatory (glutamate) to inhibitory (GABA) neurotransmitters. In contrast, glutamine supplementation significantly increased brain arginine (30% for aldh5a1+/+ and 18% for aldh5a1-/- mice), and leucine (12% and 18%). Glutamine deficiency was confirmed in the liver. The test diet increased hepatic glutamate in both genotypes, decreased glutamine in aldh5a1+/+ but not in aldh5a1-/- , but had no effect on GABA. Dried bloodspot analyses showed significantly elevated GABA in mutants (approximately 800% above controls) and decreased glutamate (approximately 25%), but no glutamine difference with controls. Glutamine supplementation did not impact blood GABA but significantly increased glutamine and glutamate in both genotypes indicating systemic exposure to dietary glutamine. Ataxia and pronounced hyperactivity were observed in aldh5a1-/- mice but remained unchanged by the diet intervention. The study suggests that glutamine supplementation improves peripheral but not central glutamine deficiency in experimental SSADHD. Future studies are needed to fully understand the pathogenic role of brain glutamine deficiency in SSADHD.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Biomarcadores/sangue , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/metabolismo , Glutamina/administração & dosagem , Succinato-Semialdeído Desidrogenase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Aminoácidos/metabolismo , Animais , Encéfalo/patologia , Deficiências do Desenvolvimento/sangue , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Succinato-Semialdeído Desidrogenase/sangue , Succinato-Semialdeído Desidrogenase/genética , Succinato-Semialdeído Desidrogenase/metabolismo , Ácido gama-Aminobutírico/metabolismo
7.
J Sleep Res ; 25(3): 257-68, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26825702

RESUMO

Markers of sleep drive (<10 Hz; slow-wave activity and theta) have been identified in the course of slow-wave sleep and wakefulness. So far, higher frequencies in the waking electroencephalogram have not been examined thoroughly as a function of sleep drive. Here, electroencephalogram dynamics were measured in epochs of active wake (wake characterized by high muscle tone) or quiet wake (wake characterized by low muscle tone). It was hypothesized that the higher beta oscillations (15-35 Hz, measured by local field potential and electroencephalography) represent fundamentally different processes in active wake and quiet wake. In active wake, sensory stimulation elevated beta activity in parallel with gamma (80-90 Hz) activity, indicative of cognitive processing. In quiet wake, beta activity paralleled slow-wave activity (1-4 Hz) and theta (5-8 Hz) in tracking sleep need. Cerebral lactate concentration, a measure of cerebral glucose utilization, increased during active wake whereas it declined during quiet wake. Mathematical modelling of state-dependent dynamics of cortical lactate concentration was more precisely predictive when quiet wake and active wake were included as two distinct substates rather than a uniform state of wakefulness. The extent to which lactate concentration declined in quiet wake and increased in active wake was proportionate to the amount of beta activity. These data distinguish quiet wake from active wake. Quiet wake, particularly when characterized by beta activity, is permissive to metabolic and electrophysiological changes that occur in slow-wave sleep. These data urge further studies on state-dependent beta oscillations across species.


Assuntos
Eletroencefalografia , Homeostase , Sono/fisiologia , Vigília/fisiologia , Animais , Ritmo beta , Ritmo Gama , Glucose/metabolismo , Ácido Láctico/metabolismo , Masculino , Camundongos , Músculos/fisiologia
8.
Brain Behav Immun ; 47: 66-74, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25542735

RESUMO

Cytokines such as TNFα play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFα gene (TNFα G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFα 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFα G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFα in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFα G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation.


Assuntos
Atenção/fisiologia , Polimorfismo de Nucleotídeo Único , Desempenho Psicomotor/fisiologia , Tempo de Reação/genética , Privação do Sono/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Nível de Alerta , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Sono/genética , Adulto Jovem
9.
Cereb Cortex ; 23(8): 1978-87, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22767634

RESUMO

Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1-4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of <10 Hz. The induction of 1-Hz oscillations, but not 10-Hz oscillations, in the electroencephalogram by optogenetic stimulation of cortical pyramidal cells during wakefulness triggers a decline in lactate concentration. We conclude that cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.


Assuntos
Córtex Cerebral/metabolismo , Glicólise , Sono/fisiologia , Animais , Ácido Láctico/metabolismo , Masculino , Camundongos , Camundongos Transgênicos
10.
Proc Natl Acad Sci U S A ; 107(2): 827-31, 2010 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-20080760

RESUMO

The intracellular signaling mechanisms regulating the generation and long-term persistence of memory T cells in vivo remain unclear. In this study, we used mouse models with conditional deletion of the key T cell receptor (TCR)-coupled adaptor molecule SH2-domain-containing phosphoprotein of 76 kDa (SLP-76), to analyze signaling mechanisms for memory CD4 T cell generation, maintenance, and homeostasis. We found that ablation of SLP-76 expression after T cell priming did not inhibit generation of phenotypic effector or memory CD4 T cells; however, the resultant SLP-76-deficient memory CD4 T cells could not produce recall cytokines in response to TCR-mediated stimulation and showed decreased persistence in vivo. In addition, SLP-76-deficient memory CD4 T cells exhibited reduced steady-state homeostasis and were impaired in their ability to homeostatically expand in vivo in response to the gamma(c) cytokine IL-7, despite intact proximal signaling through the IL-7R-coupled JAK3/STAT5 pathway. Direct in vivo deletion of SLP-76 in polyclonal memory CD4 T cells likewise led to impaired steady-state homeostasis as well as impaired homeostatic responses to IL-7. Our findings demonstrate a dominant role for SLP-76-dependent TCR signals in regulating turnover and perpetuation of memory CD4 T cells and their responses to homeostatic cytokines, with implications for the selective survival of memory CD4 T cells following pathogen exposure, vaccination, and aging.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/fisiologia , Fosfoproteínas/fisiologia , Linfócitos T/imunologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Regulação para Baixo , Técnicas de Transferência de Genes , Genes Reporter , Homeostase/genética , Homeostase/imunologia , Memória Imunológica , Interleucina-7/farmacologia , Proteínas Luminescentes/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Modelos Animais , Fosfoproteínas/deficiência , Fosfoproteínas/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia
11.
Vet Surg ; 42(3): 231-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23278565

RESUMO

OBJECTIVE: To compare the effects of triamcinolone acetonide (TA) and methylprednisolone acetate (MPA) on expression of selected chondrocyte genes in recombinant equine interleukin-1ß (reIL-1ß) stimulated articular cartilage explants. DESIGN: In vitro experiment. ANIMALS: Horses (n = 6). PROCEDURES: Articular cartilage explants from 2- to 3- year-old horses were exposed to reIL-1ß in the presence and absence of TA and MPA at 10(-7) and 10(-6) M. Resting levels of mRNA of anabolic and catabolic genes of chondrocyte origin were quantified using qPCR after 6- and 12-hour incubations. Genes of interest included aggrecan interglobular domain, aggrecan, and collagen II, matrix metalloproteinases 3 and 13 (MMP3, MMP 13), aggrecanase 1, tissue inhibitor of matrix metalloproteinases 1 and 2 (TIMP 1, TIMP 2), BCL 2, vascular endothelial growth factor, and cyclooxygenase 2 (COX 2). RESULTS: IL-1ß significantly influenced the expression of most transcripts. MPA and TA inhibited the induction of MMP 13 at 6 and 12 hours; an effect that was significant at 6 hours with MPA at 10(-7) M and TA at 10(-6) M. Similarly, COX 2 was induced by reIL-1ß and MPA and TA significantly inhibited its upregulation. TIMP 2 expression was reduced by reIL-1ß, an effect that was significantly abrogated by MPA and TA. There were no significant differences observed between glucocorticoids for any gene studied. CONCLUSIONS: No differential effects of MPA or TA on chondrocytic gene expression were identified suggesting that any divergent influences of these glucocorticoids on chondrocyte metabolism are posttranslational.


Assuntos
Corticosteroides/farmacologia , Condrócitos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/farmacologia , Metilprednisolona/análogos & derivados , Triancinolona Acetonida/farmacologia , Proteínas ADAM/biossíntese , Agrecanas/biossíntese , Animais , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/fisiologia , Condrócitos/metabolismo , Condrócitos/fisiologia , Colágeno Tipo II/biossíntese , Ciclo-Oxigenase 2/biossíntese , Cavalos , Metaloproteinase 13 da Matriz/biossíntese , Metaloproteinase 3 da Matriz/biossíntese , Metilprednisolona/farmacologia , Acetato de Metilprednisolona , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Microglobulina beta-2
12.
13.
PLoS One ; 18(6): e0287908, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37384610

RESUMO

INTRODUCTION: Practical skills training is an essential part of medical education. An important example is the training of Basic Life Support (BLS) skills, which are key to improve patient outcomes in life-threatening situations. However, despite practical training, BLS performance is often sub-optimal even among healthcare professionals and medical students. Finding more effective training methods is therefore of high importance. A promising method to enhance learning outcomes is reflective practice. The goal of the present study was to evaluate whether a short reflective practice intervention following standard BLS training (Peyton's 4-step approach) improves BLS training outcomes, reflected in higher BLS performance and higher self-confidence to perform BLS. METHOD: 287 first-year medical students were randomly assigned to one of two BLS training conditions: 1) standard BLS training (ST), 2) ST followed by a 15-minute reflective practice exercise. Outcome parameters included objective BLS performance data assessed by a resuscitation manikin, and students' self-reported confidence in their BLS skills. Outcomes were assessed directly after the training (T0) and re-assessed one week later (T1). A two-way mixed model analysis of variance (ANOVA) was conducted to examine the effect of the intervention on BLS performance and self-reported confidence. Significance was determined by two-sided 95% confidence intervals. RESULTS: The intervention group performed significantly more effective compressions at T1 and began significantly faster with performing their first chest compression at T0 and T1, in comparison to the control group. No significant differences between study groups regarding their self-reported confidence to perform BLS were observed. CONCLUSION: This research shows that standard BLS training accompanied with a simple, cost-effective reflective practice exercise can improve learners' BLS skill acquisition and retention. This shows that reflective practice has the potential to enhance practical skills training in medicine; yet, more empirical studies are needed to examine its broader applicability.


Assuntos
Medicina , Projetos de Pesquisa , Humanos , Aprendizagem , Estudantes , Grupos Controle
14.
Sleep Adv ; 4(1): zpad044, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38152423

RESUMO

Non-rapid eye movement sleep (NREMS) is accompanied by a reduction in cerebral glucose utilization. Enabling this metabolic change may be a central function of sleep. Since the reduction in glucose metabolism is inevitably accompanied by deceleration of downstream oxidation/reduction reactions involving nicotinamide adenine dinucleotide (NAD), we hypothesized a role for NAD in regulating the homeostatic dynamics of sleep at the biochemical level. We applied dietary nicotinamide riboside (NR), a NAD precursor, in a protocol known to improve neurological outcome measures in mice. Long-term (6-10 weeks) dietary supplementation with NR reduced the time that mice spent in NREMS by 17 percent and accelerated the rate of discharge of sleep need according to a mathematical model of sleep homeostasis (Process S). These findings suggest that increasing redox capacity by increasing nicotinamide availability reduces sleep need and increases the cortical capacity for energetically demanding high-frequency oscillations. In turn, this work demonstrates the impact of redox substrates on cortical circuit properties related to fatigue and sleep drive, implicating redox reactions in the homeostatic dynamics of cortical network events across sleep-wake cycles.

15.
Antioxidants (Basel) ; 12(5)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37237990

RESUMO

Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox environment may be a central function of sleep. Therefore, biochemical manipulations that potentiate cellular antioxidant pathways may facilitate this function of sleep. N-acetylcysteine increases cellular antioxidant capacity by serving as a precursor to glutathione. In mice, we observed that intraperitoneal administration of N-acetylcysteine at a time of day when sleep drive is naturally high accelerated the onset of sleep and reduced NREMS delta power. Additionally, N-acetylcysteine administration suppressed slow and beta electroencephalographic (EEG) activities during quiet wake, further demonstrating the fatigue-inducing properties of antioxidants and the impact of redox balance on cortical circuit properties related to sleep drive. These results implicate redox reactions in the homeostatic dynamics of cortical network events across sleep/wake cycles, illustrating the value of timing antioxidant administration relative to sleep/wake cycles. A systematic review of the relevant literature, summarized herein, indicates that this "chronotherapeutic hypothesis" is unaddressed within the clinical literature on antioxidant therapy for brain disorders such as schizophrenia. We, therefore, advocate for studies that systematically address the relationship between the time of day at which an antioxidant therapy is administered relative to sleep/wake cycles and the therapeutic benefit of that antioxidant treatment in brain disorders.

16.
Eur J Immunol ; 41(7): 2064-73, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21469089

RESUMO

The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76 kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T-cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of WT SLP-76 protein in thymocytes. Here, we show that following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR-generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4+ T-cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. Altogether, our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfócitos T CD4-Positivos/imunologia , Fosfoproteínas/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Linfócitos T CD4-Positivos/metabolismo , Proliferação de Células , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfoproteínas/genética , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Tamoxifeno/farmacologia
17.
Blood ; 116(25): 5560-70, 2010 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-20884806

RESUMO

The requirements for tonic T-cell receptor (TCR) signaling in CD8(+) memory T-cell generation and homeostasis are poorly defined. The SRC homology 2 (SH2)-domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for proximal TCR-generated signaling. We used temporally mediated deletion of SLP-76 to interrupt tonic and activating TCR signals after clearance of the lymphocytic choriomeningitis virus (LCMV). SLP-76-dependent signals are required during the contraction phase of the immune response for the normal generation of CD8 memory precursor cells. Conversely, LCMV-specific memory CD8 T cells generated in the presence of SLP-76 and then acutely deprived of TCR-mediated signals persist in vivo in normal numbers for more than 40 weeks. Tonic TCR signals are not required for the transition of the memory pool toward a central memory phenotype, but the absence of SLP-76 during memory homeostasis substantially alters the kinetics. Our data are consistent with a model in which tonic TCR signals are required at multiple stages of differentiation, but are dispensable for memory CD8 T-cell persistence.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Memória Imunológica , Fosfoproteínas/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia , Transdução de Sinais , Animais , Western Blotting , Linfócitos T CD8-Positivos/virologia , Proliferação de Células , Feminino , Citometria de Fluxo , Ativação Linfocitária , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/patologia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/patogenicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
18.
Front Syst Neurosci ; 16: 1052441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467979

RESUMO

Introduction: Insufficient sleep is pervasive worldwide, and its toll on health and safety is recapitulated in many settings. It is thus important to understand how poor sleep affects the brain and decision making. A robust literature documents the adverse effects of sleep deprivation on cognitive processes including cognitive flexibility, which is the capacity to appraise new feedback and make behavioral adjustments to respond appropriately. Animal models are often used to unravel the molecules, genes and neural circuits that are altered by sleep loss. Herein we take a translational approach to model the effects of sleep deprivation on cognitive rigidity, i.e., impaired cognitive flexibility in rats. Methods: There are several approaches to assess cognitive rigidity; in the present study, we employ a pairwise discrimination reversal task. To our knowledge this is the first time this paradigm has been used to investigate sleep deprivation. In this touchscreen operant platform, we trained rats to select one of two images to claim a sucrose pellet reward. If the non-rewarded image was selected the rats proceeded to a correction trial where both images were presented in the same position as before. This image presentation continued until the rat selected the correct image. Once rats reached performance criteria, the reward contingencies were reversed. In one group of rats the initial reversal session was preceded by 10 h of sleep deprivation. We compared those rats to controls with undisturbed sleep on the number of sessions to reach performance criteria, number of trials per session, response latencies, correct responses, errors, perseverative errors and perseveration bouts in the initial training and reversal phases. Results: We report that on reversal session one, sleep deprived rats completed a fraction of the trials completed by controls. On subsequent reversal sessions, the sleep deprived rats struggled to adapt to the reversed contingencies despite completing a similar number of trials, suggesting an effect of cognitive rigidity separate from fatigue. Discussion: We discuss the delayed performance dynamics incurred by sleep loss in the context of fatigue and the implications of using pairwise discrimination reversal as a model to further examine the effects of sleep loss on adaptive decision making.

19.
GMS J Med Educ ; 39(4): Doc46, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36310883

RESUMO

Introduction: Telemedicine is a significant component of healthcare in most disciplines, giving great importance to the education of young physicians in this field. However, the topic of telemedicine has not yet been implemented in medical schools' curricula. This paper makes an important contribution to closing this gap by designing, implementing and evaluating a course with telemedical components. Using the example of a clinical traineeship preparation course, we investigated the extent to which integrated telemedical modules can contribute to the subjective confidence of students with regard to knowledge and confidence in performing practical telemedical skills, such as doctor-patient communication, taking medical histories, and applying handover techniques. Project description: The course evaluation was descriptive. Subjective confidence in clinical telemedicine skills was assessed before and after completion of the course using an online questionnaire and calculated in a pre-post design using Wilcoxon's signed-rank test. Results: The course was rated "very good" (31%) and "good" (54.2%) by the vast majority of students. The results of the Wilcoxon test show significant increases in students' feelings of confidence in performing practical telemedicine skills for all items. Discussion: This study shows that telemedicine modules integrated in a digital preparatory course contribute positively to students' subjective confidence in terms of knowledge and confidence in performing practical telemedicine skills. Specifically, this paper illustrates that professional digital doctor-patient communication, digital documentation of a medical history, and handoff techniques can be learned through telemedicine course content. Conclusion: Telemedicine modules increase students' subjective confidence in performing practical telemedicine skills. Practical telemedicine course content can thus reduce uncertainty in the use of telemedicine and prepare future physicians for its use.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Telemedicina , Humanos , Currículo , Apoio ao Desenvolvimento de Recursos Humanos
20.
Front Med (Lausanne) ; 9: 825823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646961

RESUMO

Background: Sustaining Basic Life Support (BLS) training during the COVID-19 pandemic bears substantial challenges. The limited availability of highly qualified instructors and tight economic conditions complicates the delivery of these life-saving trainings. Consequently, innovative and resource-efficient approaches are needed to minimize or eliminate contagion while maintaining high training standards and managing learner anxiety related to infection risk. Methods: In a non-inferiority trial 346 first-year medical, dentistry, and physiotherapy students underwent BLS training at AIXTRA-Competence Center for Training and Patient Safety at the University Hospital RWTH Aachen. Our objectives were (1) to examine whether peer feedback BLS training supported by tele-instructors matches the learning performance of standard instructor-guided BLS training for laypersons; and (2) to minimize infection risk during BLS training. Therefore, in a parallel group design, we compared arm (1) Standard Instructor Feedback (SIF) BLS training (Historical control group of 2019) with arm (2) a Tele-Instructor Supported Peer-Feedback (TPF) BLS training (Intervention group of 2020). Both study arms were based on Peyton's 4-step approach. Before and after each training session, objective data for BLS performance (compression depth and rate) were recorded using a resuscitation manikin. We also assessed overall BLS performance via standardized instructor evaluation and student self-reports of confidence via questionnaire. Non-inferiority margins for the outcome parameters and sample size calculation were based on previous studies with SIF. Two-sided 95% confidence intervals were employed to determine significance of non-inferiority. Results: The results confirmed non-inferiority of TPF to SIF for all tested outcome parameters. A follow-up after 2 weeks found no confirmed COVID-19 infections among the participants. Conclusion: Tele-instructor supported peer feedback is a powerful alternative to in-person instructor feedback on BLS skills during a pandemic, where infection risk needs to be minimized while maximizing the quality of BLS skill learning. Trial registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00025199, Trial ID: DRKS00025199.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA