The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer cell growth and survival. ...Acting as a d-glucose mimic, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death. In addition to glycolysis inhibition, other molecular processes are also affected by 2-DG. Attempts to improve 2-DG's drug-like properties, its role as a potential adjuvant for other chemotherapeutics, and novel 2-DG analogs as promising new anticancer agents are discussed in this review.
Altered attentional processing of pain-associated stimuli-which might take the form of either avoidance or enhanced vigilance-is thought to be implicated in the development and maintenance of chronic ...pain. In contrast to reaction time tasks like the dot probe, eye tracking allows for tracking the time course of visual attention and thus differentiating early and late attentional processes. Our study aimed at investigating visual attention to emotional faces in patients with chronic musculoskeletal pain (N = 20) and matched pain-free controls (N = 20). Emotional faces (pain, angry, happy) were presented in pairs with a neutral face for 2000 ms each. Three parameters were determined: First fixation probabilities, fixation durations (overall and divided in four 500 ms intervals) and a fixation bias score as the relative fixation duration of emotional faces compared to neutral faces. There were no group differences in any of the parameters. First fixation probabilities were lower for pain faces than for angry faces. Overall, we found longer fixation duration on emotional compared to neutral faces ('emotionality bias'), which is in accord with previous research. However, significant longer fixation duration compared to the neutral face was detected only for happy and angry but not for pain faces. In addition, fixation durations as well as bias scores yielded evidence for vigilant-avoidant processing of pain faces in both groups. These results suggest that attentional bias towards pain-associated stimuli might not generally differentiate between healthy individuals and chronic pain patients. Exaggerated attentional bias in patients might occur only under specific circumstances, e.g., towards stimulus material specifically relating to the specific pain of the patients under study or under high emotional distress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 (coronavirus disease) pandemic placed a great burden on all health-care resources, especially nurses. The prevalence and underlying risk factors of affective symptoms related to the ...COVID-19 pandemic have been studied primarily among nurses in intensive care units (ICU) and emergency departments. The aim of this study was to identify at-risk nursing areas by examining the psychological and physical stress values of nurses in different functional areas.
A questionnaire with standardized items was developed to assess psychological and physical stress values. At least 50 nurses with a minimum work experience of 3 years were recruited from the ward, outpatient clinic (OC), intermediate care (IMC) unit, and operating room (OR) of the University Hospital RWTH Aachen. The participants answered the questionnaire by referring to their perceptions before and during the COVID-19 pandemic. Absolute differences and relative trends in psychological and physical stress values were compared within and across functional areas.
The ward and OR nurses experienced significant increases in workload (p < 0.001 and p = 0.004, respectively) and time stressors (p < 0.001 and p = 0.043, respectively) during the COVID-19 pandemic. Regardless of functional area, the nurses showed strong tendencies toward increases in subclinical affective symptoms. After adjustments for age, sex, working in a shift system, the treatment of patients with COVID-19, and the impact of the COVID-19 pandemic on personal life, the values for working with pleasure decreased significantly among the ward (p = 0.001) and OR nurses (p = 0.009) compared with the OC nurses. In addition, the ward (p < 0.001) and OR nurses (p = 0.024) were significantly more likely to express intent to leave their profession than OC nurses.
The IMC nurses showed good adaptation to the exacerbated situation caused by the COVID-19 pandemic. The ward nurses, followed by the OR nurses, were the most vulnerable to mental and physical exhaustion, which threatened the nurses' resilience and retention in the wake of the COVID-19 pandemic. Therefore, intervention programs must specifically address the professional and emotional needs of ward and OR nurses to prepare the health-care system for future crises.
This study employs a novel strategy for identifying points of resistance to education efforts aimed at reducing rates of child physical abuse and use of corporal punishment (CP). We analyzed online ...comments (n = 581) generated in response to media coverage of a study linking CP with increased child aggression. Most comments (71%) reflected approval of hitting children for disciplinary purposes. Reasons for this approval were rooted in beliefs linking the use of CP with positive or neutral outcomes such as: ‘I was spanked and I am okay’, spanking improves child behavior, spanking is more effective than other forms of discipline and spanking is not abuse. However, also linked with approval were more macro-ideological beliefs about society such as: today’s generation is worse off than previous ones, outside interference with parenting is wrong, one cause leads to an outcome, justifications for hitting children rooted in religious doctrine, bad parents cannot control their children and children have too much power. Our results suggest a need to better translate and disseminate empirical findings regarding the negative effects of CP to the public in a way that is highly sensitive to parents’ needs to feel in control and effective when parenting.
Non-specific low back pain (NLBP) exerts a profound impact on global health and economics. In the era of Web 3.0, digital therapeutics offer the potential to improve NLBP management. The Rise-uP ...trial introduces a digitally anchored, general practitioner (GP)-focused back pain management approach with the Kaia back pain app as the key intervention. Here, we present the 12-months evaluation of the Rise-uP trial including clinical and economic outcomes, patient satisfaction and behavioral tracking analysis.PurposeNon-specific low back pain (NLBP) exerts a profound impact on global health and economics. In the era of Web 3.0, digital therapeutics offer the potential to improve NLBP management. The Rise-uP trial introduces a digitally anchored, general practitioner (GP)-focused back pain management approach with the Kaia back pain app as the key intervention. Here, we present the 12-months evaluation of the Rise-uP trial including clinical and economic outcomes, patient satisfaction and behavioral tracking analysis.The cluster-randomized controlled study (registration number: DRKS00015048) enrolled 1237 patients, with 930 receiving treatment according to the Rise-uP approach and 307 subjected to standard of care treatment. Assessments of pain, psychological state, functional capacity, and well-being (patient-reported outcome measures; PROMs) were collected at baseline, and at 3-, 6-, and 12-months follow-up intervals. Health insurance partners AOK, DAK, and BARMER provided individual healthcare cost data. An artificial intelligence (AI)-driven behavioral tracking analysis identified distinct app usage clusters that presented all with about the same clinical outcome. Patient satisfaction (patient-reported experience measures; PREMs) was captured at the end of the trial.MethodsThe cluster-randomized controlled study (registration number: DRKS00015048) enrolled 1237 patients, with 930 receiving treatment according to the Rise-uP approach and 307 subjected to standard of care treatment. Assessments of pain, psychological state, functional capacity, and well-being (patient-reported outcome measures; PROMs) were collected at baseline, and at 3-, 6-, and 12-months follow-up intervals. Health insurance partners AOK, DAK, and BARMER provided individual healthcare cost data. An artificial intelligence (AI)-driven behavioral tracking analysis identified distinct app usage clusters that presented all with about the same clinical outcome. Patient satisfaction (patient-reported experience measures; PREMs) was captured at the end of the trial.Intention-to-treat (ITT) analysis demonstrated that the Rise-uP group experienced significantly greater pain reduction at 12 months compared to the control group (IG: -46% vs CG: -24%; p < 0.001) with only the Rise-uP group achieving a pain reduction that was clinically meaningful. Improvements in all other PROMs were notably superior in patients of the Rise-uP group. The AI analysis of app usage discerned four usage clusters. Short- to long-term usage, all produced about the same level of pain reduction. Cost-effectiveness analysis indicated a substantial economic benefit for Rise-uP.ResultsIntention-to-treat (ITT) analysis demonstrated that the Rise-uP group experienced significantly greater pain reduction at 12 months compared to the control group (IG: -46% vs CG: -24%; p < 0.001) with only the Rise-uP group achieving a pain reduction that was clinically meaningful. Improvements in all other PROMs were notably superior in patients of the Rise-uP group. The AI analysis of app usage discerned four usage clusters. Short- to long-term usage, all produced about the same level of pain reduction. Cost-effectiveness analysis indicated a substantial economic benefit for Rise-uP.The Rise-uP approach with a medical multimodal back pain app as the central element of digital treatment demonstrates both, clinical and economic superiority compared to standard of care in the management of NLBP.ConclusionThe Rise-uP approach with a medical multimodal back pain app as the central element of digital treatment demonstrates both, clinical and economic superiority compared to standard of care in the management of NLBP.
Summary
This paper shows how X‐ray computed nanotomography (CNT) can be correlated with focused ion beam time‐of‐flight secondary ion mass spectrometry (FIB‐TOF‐SIMS) tomography on the same sample to ...investigate both the morphological and elemental structure. This methodology is applicable to relatively large specimens with dimensions of several tens of microns whilst maintaining a high spatial resolution of the order of 100 nm. However, combining X‐ray CNT and FIB‐TOF‐SIMS tomography requires innovative sample preparation protocols to allow both experiments to be conducted on exactly the same sample without chemically or structurally modifying the sample between measurements. Moreover, dedicated algorithms have been developed for effective data fusion that is biased with nine degrees of freedom. This methodology has been tested using a porous and heterogeneous solid oxide fuel cell (SOFC) that has features varying in size by three orders of magnitude – from hundreds of nanometre large pores and grains to tens of micron wide functional layers.
Lay description
Deep understanding of physical and chemical properties is essential for optimizing fabrication processes and efficiency of materials and devices. Although, many characterization tools exist they each have their strengths and weaknesses and cannot provide a complete description of the structure of a material when used alone. Therefore, correlative approaches that combine two or more techniques are of increasing interest in scientific and industrial communities. In this paper we present an innovative methodology that allows the three‐dimensional morphological and chemical structure of a sample to be obtained at spatial resolutions of the order of 100 nm. This has been achieved by using the state‐of‐the‐art X‐ray Computed Nano‐Tomography (CNT) and Focused Ion Beam Time‐Of‐Flight Secondary Ion Mass Spectrometry (FIB‐TOF‐SIMS). This kind of studies have been initially dedicated to needs of microelectronics and new energy conversion devices but can be applied to any solid materials.
Non-specific low back pain (NLBP) causes an enormous burden to patients and tremendous costs for health care systems worldwide. Frequently, treatments are not oriented to existing guidelines. In the ...future, digital elements may be promising tools to support guideline-oriented treatment in a broader range of patients. The cluster-randomized controlled "Rise-uP" trial aims to support a General Practitioner (GP)-centered back pain treatment (Registration No: DRKS00015048) and includes the following digital elements: 1) electronic case report form (eCRF), 2) a treatment algorithm for guideline-based clinical decision making of GPs, 3) teleconsultation between GPs and pain specialists for patients at risk for development of chronic back pain, and 4) a multidisciplinary mobile back pain app for all patients (Kaia App).
In the Rise-uP trial, 111 GPs throughout Bavaria (southern Germany) were randomized either to the Rise-uP intervention group (IG) or the control group (CG). Rise-uP patients were treated according to the guideline-oriented Rise-uP treatment algorithm. Standard of care was applied to the CG patients with consideration given to the "National guideline for the treatment of non-specific back pain". Pain rating on the numeric rating scale was the primary outcome measure. Psychological measures (anxiety, depression, stress), functional ability, as well as physical and mental wellbeing, served as secondary outcomes. All values were assessed at the beginning of the treatment and at 3-month follow-ups.
In total, 1245 patients (IG: 933; CG: 312) with NLBP were included in the study. The Rise-uP group showed a significantly stronger pain reduction compared to the control group after 3 months (IG: M=-33.3% vs CG: M=-14.3%). The Rise-uP group was also superior in secondary outcomes. Furthermore, high-risk patients who received a teleconsultation showed a larger decrease in pain intensity (-43.5%) than CG patients (-14.3%). ANCOVA analysis showed that the impact of teleconsultation was mediated by an increased training activity in the Kaia App.
Our results show the superiority of the innovative digital treatment algorithm realized in Rise-uP, even though the CG also received relevant active treatment by their GPs. This provides clear evidence that digital treatment may be a promising tool to improve the quality of treatment of non-specific back pain. In 2021, analyses of routine data from statutory health insurances will enable us to investigate the cost-effectiveness of digital treatment.
In the years 2009–2013 the Large Hadron Collider (LHC) has been operated with the top beam energies of 3.5 and 4 TeV per proton (from 2012) instead of the nominal 7 TeV. The currents in the ...superconducting magnets were reduced accordingly. To date only seventeen beam-induced quenches have occurred; eight of them during specially designed quench tests, the others during injection. There has not been a single beam-induced quench during normal collider operation with stored beam. The conditions, however, are expected to become much more challenging after the long LHC shutdown. The magnets will be operating at near nominal currents, and in the presence of high energy and high intensity beams with a stored energy of up to 362 MJ per beam. In this paper we summarize our efforts to understand the quench levels of LHC superconducting magnets. We describe beam-loss events and dedicated experiments with beam, as well as the simulation methods used to reproduce the observable signals. The simulated energy deposition in the coils is compared to the quench levels predicted by electrothermal models, thus allowing one to validate and improve the models which are used to set beam-dump thresholds on beam-loss monitors for run 2.
Mobile health solutions are finding their way into health systems. The Kaia app has been shown to be able to reduce back pain in two studies. Since pain often comes along with disturbed sleep and ...both symptoms are strongly related we investigated whether the Kaia app training is associated with improved sleep quality.
User data of individuals with back pain were collected in two app versions (cohort 1:
= 180; cohort 2:
= 159). We analyzed the ratings of sleep quality and pain intensity on a 11-point numeric ratings scale (NRS; 0-10) both at the beginning of usage (baseline: BL) and on the individual last day of usage (follow-up: LU) within a 3-month training program.
In both cohorts, we found a significant reduction in pain intensity from BL to LU (cohort 1:
= 4.80;
= 1.59 to
= 3.75;
= 1.76, Δ
= -1.04;
= 2.12;
(158) = 6.207;
<.001/cohort 2:
= 4.20;
= 1.98 to
= 3.65;
= 1.78; Δ
= -0.50;
= 2.04;
(147) = 3.001;
= 0.003) and a significant improvement of sleep quality (cohort 1:
= 5.76;
= 2.12 to
= 6.56;
= 1.72; Δ
=
(158) = 4.310;
< 0.001/cohort 2:
= 6.08;
= 2.08 to
= 6.76;
= 1.55; Δ
= 0.67;
= 2.13; sleep:
(147) = 3.825;
< 0.001). Interestingly, improvement of sleep quality was not fully mediated by pain reduction.
Our analysis underlines the relationship between pain and sleep in the clinical context. Improvement of sleep quality came along with pain reduction and vice versa. Further study should explain the exact mechanisms of action which are associated with the improvement of both symptom parameters.
Background
The vigilance‐(attentional) avoidance hypothesis (VAH) developed for explaining phobic reactions describes an early attentional bias towards a feared stimulus followed by attentional ...avoidance of this stimulus. Such a pattern of attentional shifts might also be found when processing of pain‐related stimuli is required. The purpose of the present study was to test the VAH for pain‐associated stimuli, i.e., faces displaying pain, using the method of eye‐tracking in a pain‐free sample.
Methods
Forty‐eight healthy participants observed pictures of faces displaying pain and other emotions (anger, joy), presented concurrently with neutral faces, while their gaze behaviours were recorded continuously.
Results
Analysis of the time course of fixation durations revealed a distinct pattern for pain faces. Participants gazed at pain faces longer than at neutral faces at the beginning (up to 1000 ms) but reduced preference for pain faces increasingly thereafter (up to 2000 ms); this decline in vigilance did not occur for anger and joy faces. Strong fear of pain (Fear of Pain Questionnaire) tended to increase attentional preference for negative faces (pain, anger), a finding, which however did not reach significance.
Conclusions
We assume that initial vigilance for pain‐associated stimuli might reflect an adaptive reaction to detect a potentially harmful stimulus. Subsequently, the pain‐associated stimulus might be less attended for the purpose of mood regulation when all clear is given in this situation.
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