Dynamic association between suicidal ambivalence and suicide risk among individuals with a history of suicide attempts.

OBJECTIVE: Suicide risk is highly fluctuating. There is a need for predictors of short-term change in suicide risk to optimize risk assessment and treatment, especially among individuals who already attempted suicide. METHODS: Based on 1776 daily assessments of 16 former psychiatric inpatients with a history of suicide attempts, we examined how suicidal ambivalence and, respectively, wish to die (WTD) and wish to live (WTL) predicted same-day and change in perceived suicide risk (i.e., next-day perceived suicide risk, controlled for same-day perceived suicide risk) in multilevel regression models. Additionally, based on the assumptions of nonlinear dynamics, we examined the associations between levels of fluctuations in the WTD/WTL and perceived suicide risk within the same time period. RESULTS: Suicidal ambivalence, WTD, and a WTL significantly correlated with same-day suicide risk. Suicidal ambivalence and WTD significantly predicted change in suicide risk. Fluctuations in WTD were significantly associated with concurrent suicide risk. CONCLUSION: The results suggest that suicidal ambivalence and WTD are drivers of suicide risk among individuals who already attempted suicide. The association between fluctuations in WTD and suicide risk was small and warrants further investigation on the practical utility as a warning sign.

Surface Topology of Redox- and Thermoresponsive Nanogel Droplets.

Hydrogels are usually depicted as a homogenous polymer block with a distinct surface. While defects in the polymer structure are looked into frequently, structural irregularities on the hydrogel surface are often neglected. In this work, thin hydrogel layers of ≈100 nm thickness (nanogels) are synthesized and characterized for their structural irregularities, as they represent the surface of macrogels. The nanogels contain a main-chain responsiveness (thermo responsive) and a responsiveness in the cross-linking points (redox responsive). By combining data from ellipsometry using box-model and two-segment-model analysis, as well as atomic force microscopy, a more defined model of the nanogel surface can be developed. Starting with a more densely cross-linked network at the silica wafer surface, the density of cross-linking gradually decreases toward the hydrogel-solvent interface. Thermo-responsive behavior of the main chain affects the entire network equally as all chain segments change solubility. Cross-linker-based redox-responsiveness, on the other hand, is only governed by the inner, more cross-linked layers of the network. Such dual responsive nanogels hence allow for developing a more detailed model of a hydrogel surface from free radical polymerization. It provides a better understanding of structural defects in hydrogels and how they are affected by responsive functionalities.

Nominally identical microplastic models differ greatly in their particle-cell interactions.

Due to the abundance of microplastics in the environment, research about its possible adverse effects is increasing exponentially. Most studies investigating the effect of microplastics on cells still rely on commercially available polystyrene microspheres. However, the choice of these model microplastic particles can affect the outcome of the studies, as even nominally identical model microplastics may interact differently with cells due to different surface properties such as the surface charge. Here, we show that nominally identical polystyrene microspheres from eight different manufacturers significantly differ in their ζ-potential, which is the electrical potential of a particle in a medium at its slipping plane. The ζ-potential of the polystyrene particles is additionally altered after environmental exposure. We developed a microfluidic microscopy platform to demonstrate that the ζ-potential determines particle-cell adhesion strength. Furthermore, we find that due to this effect, the ζ-potential also strongly determines the internalization of the microplastic particles into cells. Therefore, the ζ-potential can act as a proxy of microplastic-cell interactions and may govern adverse effects reported in various organisms exposed to microplastics.

Dynamic matrices with DNA-encoded viscoelasticity for cell and organoid culture.

Three-dimensional cell and organoid cultures rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack control over key cell-instructive properties. Here we report on fully synthetic hydrogels based on DNA libraries that self-assemble with ultrahigh-molecular-weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables computationally predictable and systematic control over its viscoelasticity, thermodynamic and kinetic parameters by changing DNA sequence information. Adjustable heat activation allows homogeneous embedding of mammalian cells. Intriguingly, stress-relaxation times can be tuned over four orders of magnitude, recapitulating mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto- and haemocompatibility, and controllable degradation. DyNAtrix-based cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts and human trophoblast organoids show high viability, proliferation and morphogenesis. DyNAtrix thus represents a programmable and versatile precision matrix for advanced approaches to biomechanics, biophysics and tissue engineering.

Dynamic wetting properties of PDMS pseudo-brushes: Four-phase contact point dynamics case.

We investigate the wetting properties of PDMS (Polydimethylsiloxane) pseudo-brush anchored on glass substrates. These PDMS pseudo-brushes exhibit a significantly lower contact angle hysteresis compared to hydrophobic silanized substrates. The effect of different molar masses of the used PDMS on the wetting properties seems negligible. The surface roughness and thickness of the PDMS pseudo-brush are measured by atomic force microscopy and x-ray reflectivity. The outcome shows that these surfaces are extremely smooth (topologically and chemically), which explains the reduction in contact angle hysteresis. These special features make this kind of surfaces very useful for wetting experiments. Here, the dynamics of the four-phase contact point are studied on these surfaces. The four-phase contact point dynamics on PDMS pseudo-brushes deviate substantially from its dynamics on other substrates. These changes depend only a little on the molar mass of the used PDMS. In general, PDMS pseudo-brushes increase the traveling speed of four-phase contact point on the surface and change the associated power law of position vs time.

Critical analysis of adhesion work measurements from AFM-based techniques for soft contact.

HYPOTHESIS: The work of adhesion is a thermodynamic quantity that is frequently measured by atomic force microscopy (AFM). Determination of the work of adhesion requires quasi-equilibrium measurements, where we address the question of to what extent atomic force microscopy qualifies for quasi-equilibrium measurements. EXPERIMENT: To measure the work of adhesion, we combined soft colloidal probe AFM (SCP AFM) with reflection interference contrast microscopy (RICM). This allowed us to extract the work of adhesion either from the pull-off force or from the contact radius. With these methods, we investigated the adhesion behavior of poly(N-isopropylacrylamide) (PNIPAM) polymer brushes in the swollen and solvent-induced collapsed state by systematically analyzing contact radii and adhesive forces. FINDINGS: In the swollen state, the adhesion to the PNIPAM brush was fivefold larger and exhibited significant time dependencies when measured with SCP AFM. A strong rate dependence of the pull-off force method was indicative of a non-equilibrium process. In order to reliably determine the equilibrium work of adhesion, the contact radius method was found to be the better because it is not rate dependent. Our work highlights the important benefits of using optical measurements to determine the contact radius when deriving the works of adhesion between colloidal probes and polymer brush surfaces.

Influence of the Atmosphere on the Wettability of Polymer Brushes.

Polymer brushes, i.e., end-tethered polymer chains on substrates, are sensitive to adaptation, e.g., swelling, adsorption, and reorientation of the surface molecules. This adaptation can originate from a contacting liquid or atmosphere for partially wetted substrates. The macroscopic contact angle of the aqueous drop can depend on both adaptation mechanisms. We analyze how the atmosphere around an aqueous droplet determines the resulting contact angle of the wetting droplet on polymer brush surfaces. Poly(N-isopropylacrylamide) (PNiPAAm)-based brushes are used due to their exceptional sensitivity to solvation and liquid mixture composition. We develop a method that reliably measures wetting properties when the drop and the surrounding atmosphere are not in equilibrium, e.g., when evaporation and condensation tend to contaminate the liquid of the drop and the atmosphere. For this purpose, we use a coaxial needle in the droplet, which continuously exchanges the wetting liquid, and in addition, we constantly exchange the almost saturated atmosphere. Depending on the wetting history, PNiPAAm can be prepared in two states, state A with a large water contact angle (∼65°) and state B with a small water contact angle (∼25°). With the coaxial needle, we can demonstrate that the water contact angle of a sample in state B significantly increases by ∼30° when a water-free atmosphere is almost saturated with ethanol, compared to an ethanol-free atmosphere at 50% relative humidity. For a sample in state A, the relative humidity has little influence on the water contact angle.

Characterization in respect to degradation of titanium-coated polypropylene surgical mesh explanted from humans.

Titanium-coated polypropylene (Ti-PP) mesh was introduced in 2002 as a surgical mesh for the treatment of hernias and shortly after for pelvic floor surgery, with the aim of improving biocompatibility when compared to non-titanised/regular PP mesh implants. The application of a titanium coating could also be beneficial to address concerns regarding the exposure of PP in an in vivo environment. Many studies have shown that PP, although it is widely accepted as a stable polymer, is subject to oxidation and degradation, such degradation affects the mechanical behavior, that is, the stiffness and tensile strength of PP mesh. Despite the wide clinical use of Ti-PP surgical meshes, no study has yet investigated the residual material properties post clinical deployment and subsequent explantation. In this study, two explanted Ti-PP mesh samples each having different incorporation durations from two patients were examined. Material analysis conducted within this study includes the following techniques: attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, low voltage - scanning electron microscopy (LV-SEM), backscattered electron (BSE) imaging, energy dispersive X-ray spectroscopy (EDS) and secondary election hyperspectral imaging (SEHI). The hypothesis of this study is that the Ti coating successfully shields the PP mesh from oxidative stress in vivo and thus protects it from degradation. The results of this analysis show for the first time evidence of bulk oxidation, surface degradation, and environmental stress cracking on explanted Ti-PP meshes.

Sleep patterns in patients treated for non-secreting intra- and parasellar tumors: A self-report case-control study.

Purpose: In this study we evaluate sleep patterns of patients treated for non-secreting intra- and parasellar tumors and age- and sex-matched healthy controls. Methods: We conducted a self-report cross-sectional case-control study with 104 patients treated for non-secreting intra- and parasellar tumors and 1800 healthy controls in an 1:8 matching. All subjects answered the Munich ChronoType Questionnaire, whereas patients were provided the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Short-Form 36 Health survey, the Beck Depression Inventory and the State-Trait Anxiety Inventory additionally. Results: Patients treated for non-secreting intra- and parasellar tumors go to bed earlier, fall asleep earlier, need less time to prepare to sleep but also to get up. Additionally, they lie and sleep longer. The subgroup analysis showed that patients with secondary adrenal insufficiency compared to controls experienced shorter daily light exposure and longer sleep latency. Higher hydrocortisone dose (>20mg) was associated with worse score in global, physical and mental health, shorter time to prepare to sleep, earlier sleep onset and longer sleep duration. Conclusion: Our study shows that patients treated for non-secreting intra- and parasellar tumors, even if successfully treated, experience altered sleep patterns compared to controls. We suggest that managing clinicians should enlighten these possible sleep alterations to their patients and use specific questionnaires to document sleep disturbances. Additionally, when treating patients surgically, especially by transcranial approach, damaging the suprachiasmatic nucleus should be avoided. Furthermore, circadian hydrocortisone replacement therapy ideally with dual-release hydrocortisone - if possible, in a dose not more than 20mg daily - that resembles physiological cortisol levels more closely may be beneficial and could improve sleep patterns and sleep-related quality of life.

TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome.

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing's disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

About-Weekly Pattern in the Dynamic Complexity of a Healthy Subject's Cellular Immune Activity: A Biopsychosocial Analysis.

In a previous integrative single-case study, we collected biological, psychological and social time-series data on a 25-year-old healthy woman over the course of 126 12-h intervals (63 days) and used urinary neopterin as an indicator of cellular immune activity [Schubert et al. 2012 (1)]. The present re-evaluation introduced Dynamic Complexity (DC) as an additional non-linear and non-stationary measure to further investigate the subject's biopsychosocial dynamics during the study. The new time series dealing with urinary neopterin complexity revealed a cyclic, circaseptan (about-weekly) repeating pattern (6.59 days). The only weekly reoccurring events over the course of the study that were associated with this immunological pattern were the in-depth interviews with the subject (mean distance between interviews: 6.5 days). Superposed epoch analysis (SEA) revealed a U-shaped relation between neopterin complexity and interviews, with a decrease in neopterin complexity before and during interviews and an increase after interviews. Furthermore, the complexity scores for irritation, anxiousness/depressiveness and mental activity were positively correlated with neopterin complexity. The results suggest that the interviews, which had been found to be related to the subject's need for educational and/or social accomplishment, were marked by stress (decrease in psycho-immunological flexibility and adaptability), which was then relieved after the interviews (increase in psycho-immunological flexibility and adaptability). It appears that the subject's cellular immune activity, as indicated by neopterin complexity, functionally mirrored the emotional meaning she ascribed to the in-depth interviews. This re-evaluation is in line with the view that biopsychosocial research requires multimodal analysis of single cases based on qualitative (e.g., in-depth interviews) and quantitative (e.g., time series analysis) data under conditions of "life as it is lived".

Repulsive Interactions of Eco-corona-Covered Microplastic Particles Quantitatively Follow Modeling of Polymer Brushes.

The environmental fate and toxicity of microplastic particles are dominated by their surface properties. In the environment, an adsorbed layer of biomolecules and natural organic matter forms the so-called eco-corona. A quantitative description of how this eco-corona changes the particles' colloidal interactions is still missing. Here, we demonstrate with colloidal probe-atomic force microscopy that eco-corona formation on microplastic particles introduces a compressible film on the surface, which changes the mechanical behavior. We measure single particle-particle interactions and find a pronounced increase of long-range repulsive interactions upon eco-corona formation. These force-separation characteristics follow the Alexander-de Gennes (AdG) polymer brush model under certain conditions. We further compare the obtained fitting parameters to known systems like polyelectrolyte multilayers and propose these as model systems for the eco-corona. Our results show that concepts of fundamental polymer physics, like the AdG model, also help in understanding more complex systems like biomolecules adsorbed to surfaces, i.e., the eco-corona.

Molecular Transport within Polymer Brushes: A FRET View at Aqueous Interfaces.

Molecular permeability through polymer brush chains is implicated in surface lubrication, wettability, and solute capture and release. Probing molecular transport through polymer brushes can reveal information on the polymer nanostructure, with a permeability that is dependent on chain conformation and grafting density. Herein, we introduce a brush system to study the molecular transport of fluorophores from an aqueous droplet into the external "dry" polymer brush with the vapour phase above. The brushes consist of a random copolymer of N-isopropylacrylamide and a Förster resonance energy transfer (FRET) donor-labelled monomer, forming ultrathin brush architectures of about 35 nm in solvated height. Aqueous droplets containing a separate FRET acceptor are placed onto the surfaces, with FRET monitored spatially around the 3-phase contact line. FRET is used to monitor the transport from the droplet to the outside brush, and the changing internal distributions with time as the droplets prepare to recede. This reveals information on the dynamics and distances involved in the molecular transport of the FRET acceptor towards and away from the droplet contact line, which are strongly dependent on the relative humidity of the system. We anticipate our system to be extremely useful for studying lubrication dynamics and surface droplet wettability processes.

Concentration gradients in evaporating binary droplets probed by spatially resolved Raman and NMR spectroscopy.

Understanding the evaporation process of binary sessile droplets is essential for optimizing various technical processes, such as inkjet printing or heat transfer. Liquid mixtures whose evaporation and wetting properties may differ significantly from those of pure liquids are particularly interesting. Concentration gradients may occur in these binary droplets. The challenge is to measure concentration gradients without affecting the evaporation process. Here, spectroscopic methods with spatial resolution can discriminate between the components of a liquid mixture. We show that confocal Raman microscopy and spatially resolved NMR spectroscopy can be used as complementary methods to measure concentration gradients in evaporating 1-butanol/1-hexanol droplets on a hydrophobic surface. Deuterating one of the liquids allows analysis of the local composition through the comparison of the intensities of the C­H and C­D stretching bands in Raman spectra. Thus, a concentration gradient in the evaporating droplet was established. Spatially resolved NMR spectroscopy revealed the composition at different positions of a droplet evaporating in the NMR tube, an environment in which air exchange is less pronounced. While not being perfectly comparable, both methods­confocal Raman and spatially resolved NMR experiments­show the presence of a vertical concentration gradient as 1-butanol/1-hexanol droplets evaporate.

Mechanofluorescent Polymer Brush Surfaces that Spatially Resolve Surface Solvation.

Polymer brushes, consisting of densely end-tethered polymers to a surface, can exhibit rapid and sharp conformational transitions due to specific stimuli, which offer intriguing possibilities for surface-based sensing of the stimuli. The key toward unlocking these possibilities is the development of methods to readily transduce signals from polymer conformational changes. Herein, we report on single-fluorophore integrated ultrathin (<40 nm) polymer brush surfaces that exhibit changing fluorescence properties based on polymer conformation. The basis of our methods is the change in occupied volume as the polymer brush undergoes a collapse transition, which enhances the effective concentration and aggregation of the integrated fluorophores, leading to a self-quenching of the fluorophores' fluorescence and thereby reduced fluorescence lifetimes. By using fluorescence lifetime imaging microscopy, we reveal spatial details on polymer brush conformational transitions across complex interfaces, including at the air-water-solid interface and at the interface of immiscible liquids that solvate the surface. Furthermore, our method identifies the swelling of polymer brushes from outside of a direct droplet (i.e., the polymer phase with vapor above), which is controlled by humidity. These solvation-sensitive surfaces offer a strong potential for surface-based sensing of stimuli-induced phase transitions of polymer brushes with spatially resolved output in high resolution.

Laparoscopic versus vaginal native tissue repair in combination with pectopexy. Sub-analysis from an international, prospective, and multi-centre study: short term results.

INTRODUCTION: The use of mesh for vaginal repairs is currently problematic and as a consequence, there is increased interest in native tissue repair. We describe the follow-up data of a sub-analysis of a prospective and multi-center study focusing on the combination of pectopexy and native tissue repair. Patients were followed up for 12-18 months after surgery (+ SD: 15). Two-hundred and sixty-four patients attended the clinics for physical examination and were integrated into the follow-up. Cystocele repair was performed laparoscopically in 84 patients and vaginally in 52 patients. Posterior repair was performed vaginally in 40 patients and laparoscopically in 53 patients. RESULTS: Clinical success rate, patient recommendations and patient satisfaction rates were similar in both groups. The laparoscopic anterior repair resulted in an 89% cure or anatomical improvement rate; this compared to 94.2% for the vaginal approach. In the posterior group, laparoscopy resulted in a 94.3% cure or improvement rate compared to 97.5% in the second group. CONCLUSIONS: The outcomes of both strategies showed satisfactory results in our study. Consequently, surgeons may choose between the two strategies according to their preference and skill. The two approaches only differed with regard to vaginal scarring. We suggest future research investigating the long-term impact of scarring.

Elasticity-to-Capillarity Transition in Soft Substrate Deformation.

Whereas capillarity controls fluid dynamics at submillimeter scale and elasticity determines the mechanics of rigid solids, their coupling governs elastocapillary deformations on soft solids. Here, we directly probed the deformations on soft substrates induced by sessile nanodroplets. The wetting ridge created around the contact line and the dimple formed underneath the nanodroplet were imaged with a high spatial resolution using atomic force microscopy. The ridge height nonmonotonically depends on the substrate stiffness, and the dimple depth nonlinearly depends on the droplet size. The capillarity of the substrate overcomes the elasticity of the substrate in dominating the deformations when the elastocapillary length is approximately larger than the droplet contact radius, showing an experimental observation of the elasticity-to-capillarity transition. This study provides an experimental approach to investigate nanoscale elastocapillarity, and the insights have the potential to kick-off future work on the fundamentals of solid mechanics.

Preclinical safety testing and initial experience of a morcellation bag with four sealable ports.

Electromechanical morcellation-so called power morcellation-is a minimally invasive approach to remove bulky lesions such as uterine fibroids. The spread of benign and malignant tissue due to morcellation is a major concern that might limit the use of laparoscopic interventions. We present an in vitro evaluation of the safety characteristics of a four-port endobag with closable trocar sleeves, and describe physical properties of the bag that may or may not allow passage through the hole. In addition, we report our preliminary experience of this tool when used for laparoscopic supracervical hysterectomies. The behavior of the endobag during the extraction process was analyzed by extracting opened and re-sealed bags filled with 20 ml blue dye solution through a wooden template, with incisions measuring 10 to 24 mm. The endobag was used in 50 subtotal hysterectomies during the morcellation procedure. In the in vitro test, no dye loss was recorded for incisions measuring 11-24 mm. The mean force required to pull the bag through the template was inversely proportional to incision size. No bag rupture occurred during the surgical procedures. The mean time taken to prepare the bag for morcellation was 7.1 min (range, 4-14 min), the mean duration of subtotal hysterectomy was 53.4 min (range, 20-194 min). The mean weight of the removed body of the uterus was 113.8 g (range, 13-896 g), the mean weight of tissue and fluid remaining in the bag after morcellation 7.9 g (range, 0-39 g). In the in vitro setting, the improved endobag signifies greater patient safety during bag extraction, along with less tissue traumatization due to a smaller incision in the abdominal wall. The improved ergonomic features of the bag permit the insertion of three trocars in the lower abdomen and avoid closure of unused access ports. Our preliminary experience has shown that the device can be used under routine conditions. Failure rates will be evaluated in future studies.