RESUMEN
Introduction: Previous research suggested differential stress reactivity depending on individuals' coping style, e.g., as classified by the model of coping modes. Specifically, stronger physiological reactivity and weaker subjective stress ratings were found for repressors than for sensitizers. However, it remains to be investigated (i) whether these findings, which are largely based on social stress induction protocols, also generalize to other stressors, (ii) whether repressors vs. sensitizers also exhibit differential stress recovery following the application of a relaxation method, and (iii) which stress reactivity and recovery patterns are seen for the two remaining coping styles, i.e., fluctuating, and non-defensive copers. The current study thus examines stress reactivity in physiology and subjective ratings to a non-social stressor and the subsequent ability to relax for the four coping groups of repressors, sensitizers, fluctuating, and non-defensive copers. Methods: A total of 96 healthy participants took part in a stress induction (Mannheim Multicomponent Stress Test) and a subsequent relaxation intervention. Subjective ratings of stress and relaxation, heart rate (HR), heart rate variability (HRV), and blood pressure were assessed during the experiment. HR and blood pressure are markers of the sympathetic stress response that can be regulated by relaxation, while HRV should increase with relaxation. To investigate long-term relaxation effects, subjective ratings were also assessed on the evening of testing. Results: Despite successful stress induction, no differential responses (baseline to stress, stress to relaxation) were observed between the different coping groups on any of the measures. In contrast, a strong baseline effect was observed that persisted throughout the experiment: In general, fluctuating copers showed lower HR and higher HRV than non-defensive copers, whereas repressors reported lower subjective stress levels and higher levels of relaxation during all study phases. No differences in subjective ratings were observed in the evening of testing. Conclusion: Contrary to previous research, no differential stress reactivity pattern was observed between coping groups, which could be due to the non-social type of stressor employed in this study. The novel finding of physiological baseline differences between fluctuating and non-defensive individuals is of interest and should be further investigated in other stressor types in future research.
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Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol λ, strongly affects the survival of ALT cells. In vitro, Pol λ can promote annealing of even a single G-rich telomeric repeat to its complementary strand and use it to prime DNA synthesis. The noncoding telomeric repeat containing RNA TERRA and replication protein A negatively regulate this activity, while the Protection of Telomeres protein 1 (POT1)/TPP1 heterodimer stimulates Pol λ. Pol λ associates with telomeres and colocalizes with TPP1 in cells. In summary, our data suggest a role of Pol λ in the maintenance of telomeres by the ALT mechanism.
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Aminopeptidasas/metabolismo , ADN Polimerasa beta/metabolismo , G-Cuádruplex , Serina Proteasas/metabolismo , Homeostasis del Telómero , Proteínas de Unión a Telómeros/metabolismo , Línea Celular Tumoral , Humanos , Complejos Multiproteicos , Proteína de Replicación A/metabolismo , Complejo Shelterina , Telómero/química , Telómero/metabolismoRESUMEN
Monomethylsilanetriol (MMST), a silicon-containing compound, has been sold in dietary supplements. However, toxicological studies on its safety profile are not readily available. To assess the safety of MMST stabilized in acacia gum, a novel delivery form of MMST, in accordance with internationally accepted standards, the genotoxic potential and repeated-dose oral toxicity of Living Silica® Acacia Gum Stabilized Monomethylsilanetriol (formerly known as Orgono Acacia Gum Powder®), a food grade product consisting of 80 ± 10% acacia gum and 2.8% (SD ± 10%) elemental silicon from MMST, was investigated. A bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, an in vivo mammalian micronucleus test, and a 90-day repeated-dose oral toxicity study in rats were performed. No evidence of mutagenicity or genotoxic activity was observed under the applied test systems. In the 90-day study, male and female Hsd.Han Wistar rats were administered daily doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage. No mortality or treatment-related adverse effects were observed, and no target organs were identified. Therefore, the no observed adverse effects level (NOAEL) was determined as 2000 mg/kg bw/day (201 mg MMST/kg bw/day), the highest dose tested.
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Goma Arábiga/toxicidad , Pruebas de Mutagenicidad/métodos , Nivel sin Efectos Adversos Observados , Silicio/toxicidad , Administración Oral , Animales , Línea Celular , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Femenino , Goma Arábiga/administración & dosificación , Masculino , Ratones , Ratas , Ratas Wistar , Silicio/administración & dosificaciónRESUMEN
BACKGROUND: User acceptance is a key indicator and driver for the use and implementation of telemonitoring applications (TMA) in healthcare. Despite various positive effects that previous studies have revealed for users of TMA, there are always patients who discontinue their participation in a telemedicine study or even decline participation. There is little evidence for the reasons for non-acceptance and non-use of TMA, especially in multimorbid patients at the age of 65 and over in their home environment. To close this research gap, this sub-study focuses on patient-reported reasons for non-acceptance and non-use of TMA in the home environment. METHODS: This study follows a mixed-method approach and focuses on patients' perspective. Quantitative data collection took place via computer-assisted telephone interviews among all drop-outs and non-participants. Qualitative data were collected via semi-structured interviews with drop-out patients and non-users. Eligible patients were recruited consecutively by general practitioners, informed and included in the study according to the inclusion criteria. Amongst others, patients measured their vital signs (blood pressure, heart frequency, oxygen saturation, weight) via telemedical measures and sent them via tablet to a Care Coordination Center to ascertain the need for intervention. Collected data on non-acceptance and non-use of TMA were analyzed quantitatively and qualitatively. RESULTS: Nine general practices in two German cities included a total of 177 patients according to the inclusion criteria. During the study, 61 study participants (34.5 %) dropped out, 80 patients (31.1 %) declined participation in the study. Drop-outs and non-participants were significantly older than active participants (p=.004 and p=.001, respectively). Predominant reasons for drop-out were the lack of the perceived added value and the content-related variety of the program on the patient's tablet, the missing interest/need for telemedical monitoring as well as the time spent participating in the study. Patients living alone, single and widowed patients reported significantly more difficulties in handling the hardware (tablet) (p=.040) and the program (Motiva) (p=.013) than married and cohabiting patients. These reasons were also reported mainly by female patients, patients aged 75 years and over, and those with a low level of education. CONCLUSION: In order to increase the acceptance and the added value of TMA for patients, the individual needs of the future target group should be analyzed at the beginning of the development. To ensure maximum user centricity, individual development steps should be continuously evaluated by the target group. TMA should be adapted to the functional abilities of elderly, multimorbid patients through, e. g., an appropriate design of the content, which is tailored to patients' individual needs. TMA should be used to an appropriate degree to avoid overburdening and should fit unobtrusively into patients' usual daily routine. For patient-specific acceptance of TMA, easy handling of the telemedical measuring and input devices is as important as the variety of offers on the platform and personal contact for technical queries. Special attention should be paid to patients who live alone, women, elderly patients over 75 years of age, and poorly educated patients in order to ensure full and easy access to technology-based telemonitoring for their own healthcare.