Cognitive function in older patients and their stress challenge using different anesthesia regimes: a single center observational study.

BACKGROUND: With increasing age older patients are at higher risk for cognitive decline after surgery. Even tailored anesthesia procedures in older patients remain a high risk for postoperative cognitive disorder. Additional stress derived from anxiety and anesthesia itself can negatively impact postoperative cognitive outcomes. The objective of this study was to evaluate the impact of general versus regional anesthesia on postoperative cognitive disorder and indicators of perioperative stress in elderly undergoing surgery. METHODS: In this single center prospective study between December 2014 and November 2015, 46 patients aged 50 to 85 years undergoing dermatology surgery were enrolled. Patients were stratified by receiving general versus regional nerve anesthesia. On three consecutive days, saliva cortisol levels were analyzed three times per day. Cognitive function was assessed on the day before and the day after surgery using comprehensive neuropsychological testing of multiple cognitive functions including memory, executive function, attention and processing speed. RESULTS: Comparing the regional anesthesia group (RAG, n = 28) with the general anesthesia group (GAG, n = 18) no significant difference in the postoperative cognitive function was observed. However, patients in the GAG had significantly higher postoperative cortisol levels when compared to patients in the RAG. In both groups, a peak of cortisol value was detected on the day of surgery, which was higher in the GAG in comparison to the RAG. CONCLUSIONS: We did not observe a difference in postoperative cognitive function between patients undergoing regional or general anesthesia for dermatology surgery. However, we found lower cortisol level in the RAG. Based on these findings, future studies should investigate alternatives to reduce stress in a general anesthesia setting. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02505815.

Autonomous DNA nanostructures instructed by hierarchically concatenated chemical reaction networks.

Concatenation and communication between chemically distinct chemical reaction networks (CRNs) is an essential principle in biology for controlling dynamics of hierarchical structures. Here, to provide a model system for such biological systems, we demonstrate autonomous lifecycles of DNA nanotubes (DNTs) by two concatenated CRNs using different thermodynamic principles: (1) ATP-powered ligation/restriction of DNA components and (2) input strand-mediated DNA strand displacement (DSD) using energy gains provided in DNA toeholds. This allows to achieve hierarchical non-equilibrium systems by concurrent ATP-powered ligation-induced DSD for activating DNT self-assembly and restriction-induced backward DSD reactions for triggering DNT degradation. We introduce indirect and direct activation of DNT self-assemblies, and orthogonal molecular recognition allows ATP-fueled self-sorting of transient multicomponent DNTs. Coupling ATP dissipation to DNA nanostructures via programmable DSD is a generic concept which should be widely applicable to organize other DNA nanostructures, and enable the design of automatons and life-like systems of higher structural complexity.

Short term cognitive function after sevoflurane anesthesia in patients suspect to obstructive sleep apnea syndrome: an observational study.

BACKGROUND: The obstructive sleep apnea syndrome (OSAS) is characterized by intermittent cerebral hypoxia which can cause cognitive alterations. Likewise, hypoxia induced neurocognitive deficits are detectable after general anesthesia using volatile anesthetics. The objective of this study was to evaluate the association between a moderate to high risk patients of OSAS and postoperative cognitive dysfunction after volatile anesthesia. METHODS: In this single center prospective, observational study between May 2013 and September 2013, 46 patients aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing surgery were enrolled. Patients were screened using the STOP-BANG test with score of 3 or higher indicating moderate to high risk of OSAS. The cognitive function was assessed using a neuropsychological assessment battery, including the DemTect test for cognitive impairment among other tests e.g. SKT memory, the day before surgery and within 2 days after extubation. RESULTS: Twenty-three of the 46 analyzed patients were identified with a moderate to high risk of OSAS. When comparing post- to preoperative phase a significant better performance for the SKT was found for both groups (p <  0.001). While the moderate to high risk group scores increased postoperative in the DemTect test, they decreased in the low risk group (p <  0.003). When comparing the changes between groups, the moderate to high risk patients showed significant better test result for DemTect testing after anaesthesia. This effect remained robust when adjusting for potential confounding variables using a two-factor ANOVA. CONCLUSION: Compared to low risk, a moderate to high risk of OSAS based on the STOP-BANG score was associated with improved postoperative cognitive function measured by the DemTect test. TRIAL REGISTRATION: The study was approved by the local Ethics committee (Ethikkommission der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany) (reference number: 87_12 B ) on 19.04.2012.

CortiLove: A pilot study on hair steroids in the context of being in love and separation.

While romantic infatuation and separation influence psychological and physiological functioning, the hypothalamic-pituitary-adrenal axis with its biomarkers cortisol, dehydroepiandrosterone (DHEA), and progesterone central for coping and distress has been scarcely researched in this context. In particular, endocrine hair analyses assumed to be more valid than saliva or blood assessments for studying long-term processes have not yet been conducted in the context of romantic love. Thus, 101 female subjects in phases of infatuation (n = 16), separation (n = 14), long-term relationships (n = 40), and singlehood (n = 31) reported psychological distress and provided 1 cm hair samples for the assessment of long-term integrated cortisol, DHEA, and progesterone over the last month. Separated, infatuated, and single women exhibited higher cortisol levels than those in a long-term relationship (all ps ≤ .031), while self-reported distress was only evident in separated individuals. Further, no group differences for progesterone (p = .602), but higher DHEA levels in the separation (p = .009) and single group (p = .016) compared to the long-term relationship group were detected. This is the first study showing that compared to women in long-term relationships, infatuation, separation, and single groups exhibit higher levels of physiological, but not necessarily self-reported indicators of distress. These findings, albeit on a very small and preliminary sample, are discussed in the context of the stress-buffering effect of relationships, and provide important starting points for bigger, more balanced studies combining multimodal self-report and biological markers in psychological research of romantic love.

ATP-Responsive and ATP-Fueled Self-Assembling Systems and Materials.

Adenosine triphosphate (ATP) is a central metabolite that plays an indispensable role in various cellular processes, from energy supply to cell-to-cell signaling. Nature has developed sophisticated strategies to use the energy stored in ATP for many metabolic and non-equilibrium processes, and to sense and bind ATP for biological signaling. The variations in the ATP concentrations from one organelle to another, from extracellular to intracellular environments, and from normal cells to cancer cells are one motivation for designing ATP-triggered and ATP-fueled systems and materials, because they show great potential for applications in biological systems by using ATP as a trigger or chemical fuel. Over the last decade, ATP has been emerging as an attractive co-assembling component for man-made stimuli-responsive as well as for fuel-driven active systems and materials. Herein, current advances and emerging concepts for ATP-triggered and ATP-fueled self-assemblies and materials are discussed, shedding light on applications and highlighting future developments. By bringing together concepts of different domains, that is from supramolecular chemistry to DNA nanoscience, from equilibrium to non-equilibrium self-assembly, and from fundamental sciences to applications, the aim is to cross-fertilize current approaches with the ultimate aim to bring synthetic ATP-dependent systems closer to living systems.

ATP-powered molecular recognition to engineer transient multivalency and self-sorting 4D hierarchical systems.

Biological systems organize multiple hierarchical structures in parallel, and create dynamic assemblies and functions by energy dissipation. In contrast, emerging artificial non-equilibrium self-assembling systems have remained relatively simplistic concerning hierarchical design, and non-equilibrium multi-component systems are uncharted territory. Here we report a modular DNA toolbox allowing to program transient non-equilibrium multicomponent systems across hierarchical length scales by introducing chemically fueled molecular recognition orchestrated by reaction networks of concurrent ATP-powered ligation and cleavage of freely programmable DNA building blocks. Going across hierarchical levels, we demonstrate transient side-chain functionalized nucleic acid polymers, and further introduce the concept of transient cooperative multivalency as a key to bridge length scales to pioneer fuel-driven encapsulation, self-assembly of colloids, and non-equilibrium transient narcissistic colloidal self-sorting on a systems level. The fully programmable and functionalizable DNA components pave the way to design chemically fueled 4D (3 space, 1 time) molecular multicomponent systems and autonomous materials.

The Relation Between Steroid Secretion Patterns and the Androgen Receptor Gene Polymorphism on Physical Health and Psychological Well-Being-Longitudinal Findings From the Men's Health 40+ Study.

Research is increasingly focusing on promoting healthy aging and the related extension of the health span by targeting crucial biological processes responsible for age-related conditions. While age-related gradual changes in steroid hormones such as testosterone, estradiol, or cortisol are well described in men, their interactions among each other or with genetic markers have not been sufficiently investigated with regard to physical health or psychological well-being. More specifically, the examination of age-related alterations in hormone interactions and the androgen receptor polymorphism, which modulates androgen action on target cells, in relation to physical health and psychological well-being represents a promising avenue for research on healthy aging in men. A total of 97 healthy aging men provided complete data on psychometric health measures as well as hormonal and genetic parameters at baseline and a 4-year follow-up assessment. Fasting saliva samples were taken at 8:00 am under standardized laboratory conditions, while the androgen receptor gene polymorphism was analyzed from dried blood spots. Longitudinal analyses revealed that psychological well-being and physical health remained stable over time. Analyses indicated that E2 moderated the course of psychological well-being, while the androgen receptor gene polymorphism moderated the course of physical health. Further, T was a strong predictor of physical health. These results suggest that the hypothalamic-pituitary-gonadal (HPG) axis might be important for the maintenance of psychological well-being in men, while physical health depends more on interindividual differences in the androgen receptor gene and T.

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids.

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte-like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use.

Service based comparison of group cognitive behavior therapy to waiting list control for chronic fatigue syndrome with regard to symptom reduction and positive psychological dimensions.

BACKGROUND: Although chronic fatigue syndrome (CFS) sometimes referred to as myalgic encephalomyelitis (ME) is a very challenging condition to treat, there is evidence that individual cognitive behavioral therapy (ICBT) can be effective for treatment and management of its symptoms. Furthermore, group cognitive behavioral therapy (GCBT) is emerging as promising treatment for the condition.The aim of the present study was to explore further the effectiveness of GCBT in a routine clinical setting and to investigate associated positive psychological effects related to GCBT. METHODS: In this pragmatic, non-randomized, controlled trial, 28 people acted as their own waiting list control by completing a range of measures 8 weeks prior to taking part in the GCBT. The intervention consisted of 8 consecutive weeks of 2.5-hour sessions. RESULTS: Repeated measures analysis of covariance revealed significant improvements in physical fatigue (F = 28.31, P < .01, effect size d = 0.52), mental fatigue (F = 7.72, P < .01, effect size d = 0.22), and depressive symptoms (Beck depression inventory-fast screen for medical individuals [BDI-FS]: F = 11.43, P < .01, effect size d = 0.30; hospital anxiety and depression scale [HADS-D]: F = 16.72, P < .01, effect size d = 0.38) compared with the waiting list. Improvements in quality of life (F = 7.56, P < .01, effect size d = 0.23), hope (F = 15.15, P < .01, effect size d = 0.36), and optimism (F = 8.17, P < .01, effect size d = 0.23) were also identified, but no change was reported for anxiety levels. Global outcome measures revealed that the majority of the individuals found the treatment beneficial and were satisfied with the results. CONCLUSION: GCBT is a beneficial and cost-effective treatment that individuals find amenable in routine clinical practice for CFS. Additionally we have described important effects emerged on positive psychological dimensions such as hope and optimism potentially enhancing the overall benefit.

Programmable dynamic steady states in ATP-driven nonequilibrium DNA systems.

Inspired by the dynamics of the dissipative self-assembly of microtubules, chemically fueled synthetic systems with transient lifetimes are emerging for nonequilibrium materials design. However, realizing programmable or even adaptive structural dynamics has proven challenging because it requires synchronization of energy uptake and dissipation events within true steady states, which remains difficult to orthogonally control in supramolecular systems. Here, we demonstrate full synchronization of both events by ATP-fueled activation and dynamization of covalent DNA bonds via an enzymatic reaction network of concurrent ligation and cleavage. Critically, the average bond ratio and the frequency of bond exchange are imprinted into the energy dissipation kinetics of the network and tunable through its constituents. We introduce temporally and structurally programmable dynamics by polymerization of transient, dynamic covalent DNA polymers with adaptive steady-state properties in dependence of ATP fuel and enzyme concentrations. This approach enables generic access to nonequilibrium soft matter systems with adaptive and programmable dynamics.

Exceptionally Ductile and Tough Biomimetic Artificial Nacre with Gas Barrier Function.

Synthetic mimics of natural high-performance structural materials have shown great and partly unforeseen opportunities for the design of multifunctional materials. For nacre-mimetic nanocomposites, it has remained extraordinarily challenging to make ductile materials with high stretchability at high fractions of reinforcements, which is however of crucial importance for flexible barrier materials. Here, highly ductile and tough nacre-mimetic nanocomposites are presented, by implementing weak, but many hydrogen bonds in a ternary nacre-mimetic system consisting of two polymers (poly(vinyl amine) and poly(vinyl alcohol)) and natural nanoclay (montmorillonite) to provide efficient energy dissipation and slippage at high nanoclay content (50 wt%). Tailored interactions enable exceptional combinations of ductility (close to 50% strain) and toughness (up to 27.5 MJ m-3 ). Extensive stress whitening, a clear sign of high internal dynamics at high internal cohesion, can be observed during mechanical deformation, and the materials can be folded like paper into origami planes without fracture. Overall, the new levels of ductility and toughness are unprecedented in highly reinforced bioinspired nanocomposites and are of critical importance to future applications, e.g., as barrier materials needed for encapsulation and as a printing substrate for flexible organic electronics.

Psychobiological Protective Factors Modifying the Association Between Age and Sexual Health in Men: Findings From the Men's Health 40+ Study.

Sexual health severely decreases with age. For males older than 40 years, erectile dysfunction (ED) is the most common sexual disorder. Although physical and psychological risk factors for ED have been identified, protective factors are yet to be determined. To date, no study has examined endocrine and psychosocial factors in parallel with regard to their modifying effect on the age-related increase in ED. Two hundred and seventy-one self-reporting healthy men aged between 40 and 75 years provided both psychometric data on sexual function and a set of potential psychosocial protective factors, and saliva samples for the analysis of steroid hormones and proinflammatory cytokines. Around 35% of the participants reported at least a mild form of ED. Direct associations with ED were identified for perceived general health, emotional support, relationship quality, intimacy motivation but not for steroid hormones or proinflammatory markers. Moderation analyses for the association between age and ED revealed positive effects for testosterone (T), dehydroepiandrosterone (DHEA), perceived general health, emotional support, intimacy motivation, and a negative effect for interleukin-6 (all p < .05; f2 > .17). Group differences between older men with and without ED emerged for T, DHEA, and psychometric measures such as perceived general health, emotional support, satisfaction with life, and intimacy motivation (all p < .05; d > .3). Both psychosocial and endocrine parameters moderated the association between age and sexual health. Perceived general health, emotional support, intimacy motivation, and relationship quality emerged as psychosocial protective factors against ED. Higher T and DHEA and lower interleukin-6 levels also buffered against an age-related increase in ED.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

Celebrating Soft Matter's 10th Anniversary: Approaches to program the time domain of self-assemblies.

Self-regulating reconfigurable soft matter systems are of great interest for creating adaptive and active material properties. Such complex functionalities emerge from non-linear and interactive behavior in space and time as demonstrated by a plethora of dynamic, self-organizing biological structures (e.g., the cytoskeleton). In man-made self-assemblies, patterning of the spatial domain has advanced to creating hierarchical structures via precise molecular programming. However, orchestration of the time domain of self-assemblies is still in its infancy and lacks universal design principles. In this Emerging Area article we outline major strategies for programming the time domain of self-assemblies following the concepts of regulatory reaction networks, energy dissipation and kinetic control. Such concepts operate outside thermodynamic equilibrium and pave the way for temporally patterned, dynamic, and autonomously acting functional materials.

Bioactive gyroid scaffolds formed by sacrificial templating of nanocellulose and nanochitin hydrogels as instructive platforms for biomimetic tissue engineering.

A sacrificial templating process using lithographically printed minimal surface structures allows complex de novo geo-metries of delicate hydrogel materials. The hydrogel scaffolds based on cellulose and chitin nanofibrils show differences in terms of attachment of human mesenchymal stem cells, and allow their differentiation into osteogenic outcomes. The approach here serves as a first example toward designer hydrogel scaffolds viable for biomimetic tissue engineering.

Incidence of perioperative sleep-disordered breathing in patients undergoing major surgery: a prospective cohort study.

BACKGROUND: Major surgery might have a modulating effect on nocturnal breathing patterns. The incidence and course of perioperative sleep-disordered breathing in individuals without a previous diagnosis of obstructive sleep apnea has not been investigated sufficiently so far. METHODS: In this study, polygraphic recordings have been obtained from 37 inpatients without a diagnosis of obstructive sleep apnea syndrome during the preoperative night before and six nights following major surgical procedures. Eligible patients consenting to participate in this study underwent polygraphic recordings including four items (O2-saturation, pulse, nasal air flow and snoring) during the study period. Polygraphic data obtained from the postoperative recordings were compared to preoperative recordings. RESULTS: Median (IQR [range]) apnea-hypopnea-index (AHI) for the whole group was 6,0 (2,5 - 14,7 [0-32,6]) in the preoperative night and increased in the following six nights post surgery: second night: 5,6 (2,6-15,0 [1,1 - 59,3]); third night: 16,9 (5,6 - 38,8 [2,9 - 64,3]); fourth night: 11,6 (5,9 - 17,3 [0,4 - 39,3]); fifth night: 15,2 (5,7 - 22,2 [0,2 - 55,5]); sixth night: 22,5 (5,2 - 35,4 [0,2 - 67,7]). AHI-scores of the third to sixth night post surgery differed significantly from data observed in the preoperative night. CONCLUSION: A significant increase in the AHI occurred frequently after major surgical procedures in the late postoperative period. Sleep-disordered breathings in the late postoperative period deserve attention, as they potentially increase the risk of postoperative complications.

Pediatric patients with disabilities--assessment of satisfaction with anesthesia.

BACKGROUND: Opinions about satisfaction with care are rarely obtained from disabled children and their carers, and few studies of this type exist in the area of pediatric anesthesia. We specifically aimed to assess groups of children with disabilities and Down syndrome and aimed to identify factors influencing satisfaction in these groups. METHODS: We assessed two groups of children using the Paediatric Perianesthesia Questionnaire (PPQ). Families with Down syndrome children (Down syndrome group, DSG) were approached via a Down syndrome family support magazine, and families with disabled children were enrolled in hospitals. Two hundred and fifteen disabled children (125 from the journal, 90 from the hospitals) were compared to matching controls without disabilities. Controls were drawn randomly using computer-generated tables of random numbers using data from the PPQ validation, to match cases for confounding variables. RESULTS: Satisfaction was lower in both groups with disabilities (P < 0.05) (lowest in the DSG), fewer would choose the hospital or anesthetic department again. In both of the disabled groups, negative comments were related to the anesthetists' behavior during the consultation, the content of the consultation, and how anxiety was dealt with. Ninety five percent in the DSG reported that the anesthetist had not mentioned or enquired about atlantoaxial instability. Satisfaction was lower than the rest of the respective group if memories of the disclosure of the disabling condition were negative (P = 0.006) or if potential offensive terms had been used during the consultation (P < 0.001). CONCLUSIONS: This is the first study to assess families with disabled children for satisfaction with anesthesia. Our findings suggest that parents of children with disabilities are less satisfied with their anesthetic care than parents of children without disabilities. Potential bias comes from the self-selection of the DSG and the recall period in this group.

[Muscle relaxants and neuromuscular monitoring - Introduction for a safe clinical application]. / Muskelrelaxanzien und neuromuskuläres Monitoring - Einführung für eine sichere klinische Anwendung.

The use of muscle relaxants facilitates endotracheal intubation and ameliorates the conditions of surgery. But, their use should be controlled - otherwise there will be postoperative residual curarisation which can lead to patient discomfort up to severe medical complications. Therefore, an appropriate surveillance via objective neuromuscular monitoring is essential. This article gives a review of the basic principles of muscle relaxants, their clinical application and the surveillance of their effects and degradation.

Clay nanopaper with tough cellulose nanofiber matrix for fire retardancy and gas barrier functions.

Nacre-mimicking hybrids of high inorganic content (>50 wt %) tend to show low strain-to-failure. Therefore, we prepared clay nanopaper hybrid composite montmorillonite platelets in a continuous matrix of nanofibrillated cellulose (NFC) with the aim of harnessing the intrinsic toughness of fibrillar networks. Hydrocolloid mixtures were used in a filtration approach akin to paper processing. The resulting multilayered structure of the nanopaper was studied by FE-SEM, FTIR, and XRD. Uniaxial stress-strain curves measured in tension and thermal analysis were carried out by DMTA and TGA. In addition, fire retardance and oxygen permeability characteristics were measured. The continuous NFC matrix is a new concept and provides unusual ductility to the nanocomposite, allowing inorganic contents as high as 90% by weight. Clay nanopaper extends the property range of cellulose nanopaper and is of interest in self-extinguishing composites and in oxygen barrier layers.