Metal-organic frameworks and covalent organic frameworks as disruptive membrane materials for energy-efficient gas separation.

In this Review we survey the molecular sieving behaviour of metal-organic framework (MOF) and covalent organic framework (COF) membranes, which is different from that of classical zeolite membranes. The nature of MOFs as inorganic-organic hybrid materials and COFs as purely organic materials is powerful and disruptive for the field of gas separation membranes. The possibility of growing neat MOFs and COFs on membrane supports, while also allowing successful blending into polymer-filler composites, has a huge advantage over classical zeolite molecular sieves. MOFs and COFs allow synthetic access to more than 100,000 different structures and tailor-made molecular gates. Additionally, soft evacuation below 100 °C is often enough to achieve pore activation. Therefore, a huge number of synthetic methods for supported MOF and COF membrane thin films, such as solvothermal synthesis, seed-mediated growth and counterdiffusion, exist. Among them, methods with high scale-up potential, for example, layer-by-layer dip- and spray-coating, chemical and physical vapour deposition, and electrochemical methods. Additionally, physical methods have been developed that involve external stimuli, such as electric fields and light. A particularly important point is their ability to react to stimuli, which has allowed the 'drawbacks' of the non-ideality of the molecular sieving properties to be exploited in a completely novel research direction. Controllable gas transport through membrane films is a next-level property of MOFs and COFs, leading towards adaptive process deviation. MOF and COF particles are highly compatible with polymers, which allows for mixed-matrix membranes. However, these membranes are not simple MOF-polymer blends, as they require improved polymer-filler interactions, such as cross-linking or surface functionalization.

Measurement of canine Th17 cells by flow cytometry.

Th17 cells are T helper cells which play an important role during inflammation and autoimmune disease. To investigate the role of these cells in diseases in dogs in a clinical setting, methods for fast identification had to be established. Th17 cells are a rare cell population, for their measurement stimulation is recommended. To examine more samples simultaneously and to receive a relatively high purity of cell population of CD3 + CD4+ cells, different methods on various levels of preselection of cells as well as the possibility of storing blood overnight for measuring Th17 cells by flow cytometry were investigated. Firstly, to receive a high number of mononuclear cells, two different density gradients were compared and analysed. Furthermore, the enrichment of CD3 + CD4+ cells via depletion of CD8alpha+, CD11b + and CD21+ cells by cell sorting (autoMACS Pro Separator) was tested. It was also investigated whether stimulation processes led to better interpretation of results and whether there was a significant difference in measurement of directly processed blood samples and samples that had been stored overnight. In conclusion, the use of the density gradient (Lymph24+ Spin Medium) resulted in a purer cell population through a significant decrease in polymorphonuclear cells (*p = 0.01). After cell sorting, a significant difference in cell population purity was detected. Within the target fraction (containing mainly CD3 + CD4+ cells), CD8alpha+, CD21+, CD11b + cell percentages were significantly lower (***p < 0.001, *p < 0.02, ***p < .0001, respectively), and CD3 + CD4+ cell percentage was significantly higher (***p < .0001). There was a significant difference in Th17 cell percentage between unstimulated and stimulated cell populations (***p < .0001), but no significant difference in the percentage of unstimulated Th17 cells (p = 0.29) or stimulated Th17 cells (p = 0.71) in stored blood in comparison to directly processed EDTA blood samples. Finally, a modified protocol that offers an efficient way to investigate samples that were stored overnight by means of flow cytometry was evolved to research the role of Th17 cells in dogs with different diseases or in healthy populations.

[Screening for depersonalization-derealization with two items of the cambridge depersonalization scale]. / Screening nach Depersonalisation-Derealisation mittels zweier Items der Cambridge Depersonalisation Scale.

Depersonalization (DP) and derealization (DR) are considered to be highly underdiagnosed. Therefore the development of screening instruments is important. From the Cambridge Depersonalization Scale (CDS) two items were extracted discriminating best patients with clinical significant DP from patients without DP. These two Items were assembled to a short version of the CDS. This short version (CDS-2) was tested in a sample of 38 patients with clinical significant DP-DR and 49 patients without or only mild DP-DR. Scores were compared against clinical diagnoses based on a structured interview (gold standard). The CDS-2 was able to differentiate patients with clinical significant DP well from other groups (cut-off of CDS-2>or=3, sensitivity=78.9%, specifity=85.7%) and also showed high reliability (Cronbachs alpha=0.92). Therefore the CDS-2 can be considered as a useful tool for screening and identification of DP-DR.

The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents.

Monofunctional alkylating agents like methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are potent inducers of cellular stress leading to chromosomal aberrations, point mutations, and cell killing. We show that these agents induce a specific cellular stress response program which includes the activation of Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPKs), p38 mitogen-activated protein kinase, and the upstream kinase SEK1/MKK4 and which depends on the reaction mechanism of the alkylating agent in question. Similar to another inducer of cellular stress, UV irradiation, damage of nuclear DNA by alkylation is not involved in the MMS-induced response. However, in contrast to UV and other inducers of the JNK/SAPKs and p38 pathways, activation of growth factor and G-protein-coupled receptors does not play a role in the MMS response. We identified the intracellular glutathione (GSH) level as critical for JNK/SAPK activation by MMS: enhancing the GSH level by pretreatment of the cells with GSH or N-acetylcysteine inhibits, whereas depletion of the cellular GSH pool causes hyperinduction of JNK/SAPK activity by MMS. In light of the JNK/SAPK-dependent induction of c-jun and c-fos transcription, and the Jun/Fos-induced transcription of xenobiotic-metabolizing enzymes, these data provide a potential critical role of JNK/SAPK and p38 in the induction of a cellular defense program against cytotoxic xenobiotics such as MMS.

Defibrillation of soft porous metal-organic frameworks with electric fields.

Gas transport through metal-organic framework membranes (MOFs) was switched in situ by applying an external electric field (E-field). The switching of gas permeation upon E-field polarization could be explained by the structural transformation of the zeolitic imidazolate framework ZIF-8 into polymorphs with more rigid lattices. Permeation measurements under a direct-current E-field poling of 500 volts per millimeter showed reversibly controlled switching of the ZIF-8 into polar polymorphs, which was confirmed by x-ray diffraction and ab initio calculations. The stiffening of the lattice causes a reduction in gas transport through the membrane and sharpens the molecular sieving capability. Dielectric spectroscopy, polarization, and deuterium nuclear magnetic resonance studies revealed low-frequency resonances of ZIF-8 that we attribute to lattice flexibility and linker movement. Upon E-field polarization, we observed a defibrillation of the different lattice motions.

UV-induced signal transduction.

Irradiation of cells with wavelength ultraviolet (UVA, B and C) induces the transcription of many genes. The program overlaps with that induced by oxidants and alkylating agents and has both protective and other functions. Genes transcribed in response to UV irradiation include genes encoding transcription factors, proteases and viral proteins. While the transcription factor encoding genes is initiated in minutes after UV irradiation (immediate response genes) and depends exclusively on performed proteins, the transcription of protease encoding occurs only many hours after UV irradiation. Transcription factors controlling the activity of immediate response genes are activated by protein kinases belonging to the group of proline directed protein kinases immediately after UV irradiation. Experimental evidence suggests that these kinases are activated in UV irradiated cells through pathways which are used by growth factors. In fact, the first cellular reaction detectable in UV irradiated cells is the phosphorylation of several growth factor receptors at tyrosine residues. This phosphorylation does not depend on UV induced DNA damage, but is due to an inhibition of the activity of tyrosine phosphatases. In contrast, for late cellular reactions to UV, an obligatory role of DNA damage in transcribed regions of the genome can be demonstrated. Thus, UV is absorbed by several target molecules relevant for cellular signaling, and it appears that numerous signal transduction pathways are stimulated. The combined action of these pathways establishes the genetic program that determines the fate of UV irradiated cells.

When weaning from mechanical ventilation fails.

OBJECTIVE: To describe the etiologies and indicators of weaning failure and to provide a framework for planning interventions to facilitate weaning of long-term ventilation patients. DATA SOURCE: A Medline search of human studies in English on weaning from mechanical ventilation. ARTICLE SELECTION: Articles were selected if they pertained to the assessment and management of weaning failure. Both research and review articles were included. DATA EXTRACTION: All pertinent articles were described, along with their limitations. DATA SYNTHESIS: Weaning from mechanical ventilation is an emerging science. Caring for patients who are difficult to wean requires expert clinical decision making so patients do not feel defeated and have the best chances for success. Combining the limited research on weaning intervention with clinical expertise helps to build a scientific basis for care and can assist clinicians in tailoring interventions to specific problems that precipitate weaning failure. CONCLUSION: A scientific approach to care may promote weaning in difficult cases and provide directions for future research into the etiologies of weaning failure.

Clinical evaluation of noninvasive monitoring of oxygen saturation in critically ill patients.

OBJECTIVE: To examine the effect of abnormal cardiac index on the accuracy of measurement of oxygen saturation by pulse oximetry. METHODS: Forty-six patients (mean age, 49 years) in a 9-bed medical ICU were studied. Measurements of oxygen saturation obtained with pulse oximeters and with a functional cooximeter were collected at baseline and 4, 8, 16, 24, 32, 40, and 48 hours later. Hemodynamic and cardiopulmonary parameters were recorded. RESULTS: The Bland-Altman technique yielded upper and lower limits of agreement of 2.53% and -7.11%. Most (95.7%) of the differences between the measurements of oxygen saturation obtained with the 2 methods were within these limits, although some of these differences may be clinically unacceptable. The bias was -2.29%, and the precision was 2.41%. The clinical conditions associated with inaccurate tracking of saturation by pulse oximetry across the range of actual arterial oxygen saturation values were abnormal cardiac index, partial pressure of carbon dioxide, heart rate, and pulmonary capillary wedge pressure. CONCLUSIONS: In patients with abnormal cardiac index, the pulse oximeter measurements exceeded the actual oxygen saturation by up to 7%. Pending prospective studies, clinicians should be aware that when certain cardiopulmonary parameters are abnormal, the margin of error in measurements of oxygen saturation obtained with a pulse oximeter may be greater than when those parameters are normal.

Weaning from mechanical ventilatory support: refinement of a model.

The American Association of Critical-Care Nurses sponsored the third National Study Group to advance the science of weaning from mechanical ventilatory support and to guide clinical practice. The study group proposed a model of weaning in 1994 to provide an organizing framework for scientific inquiry. Since the model was first proposed, the ongoing work of the study group has led to refinement of the model. The purpose of this brief communication is to inform critical care clinicians and researchers about the refinements.

Weaning from mechanical ventilation: concept development.

This article, the first in a series, is written to clarify the process of weaning from mechanical ventilation and to promote the development of a common language for understanding the complex weaning process. The Third National Study Group on Weaning From Mechanical Ventilation proposes a conceptual model and definitions that will provide a framework for future research on this important topic. This conceptual framework describes the preweaning phase, the weaning process, and the outcome phase of mechanical ventilation. Potential outcomes are completion of weaning, lack of completion, and terminal weaning. The weaning decision continuum incorporates: (1) when and how to begin the weaning process, (2) how to select therapies to assist with difficult weaning and chart progress during weaning, and (3) when to stop weaning if progress is no longer being made. An inherent assumption of this model is that each patient will display unique responses to the weaning process. The proposed conceptual framework and definitions provide a foundation for developing clinical practice guidelines and for guiding future ventilator weaning research.

Weaning from short-term mechanical ventilation: a review.

The purposes of this article are to: identify gaps in the research literature on weaning adult patients from short-term mechanical ventilation, highlight the scientific base for practice guidelines, and suggest future research directions. Data bases from 1989 through June 1993 were reviewed, and relevant research articles were extracted, analyzed, and synthesized within the AACN Third National Study Group framework. Seminal work and other supportive literature also were used in this review. Despite considerable research on predictors and patient responses to weaning from short-term mechanical ventilation, few of the findings can be applied to clinical practice at this time. Less research is available on weaning modes and therapies that facilitate weaning from short-term mechanical ventilation; fruitful research in these areas depends in part on a better understanding of patient responses and accurate weaning predictors.

Weaning from long-term mechanical ventilation.

Although many investigators have attempted to identify weaning predictors and weaning modes for use in long-term mechanically ventilated patients, none has emerged as superior. Furthermore, few investigators have viewed the process of weaning as a dynamic continuum; thus, guidelines for care of these patients have yet to be developed. Facilitative methods and therapies to enhance weaning potential, although attractive, have little scientific basis for application. Care delivery systems, which focus on systematic, comprehensive and coordinated care, are promising because outcomes demonstrate that they are economical, safe, and effective. This article reviews the research on weaning adult, long-term mechanically ventilated patients, suggests future research directions, and highlights the scientific basis for practice guidelines.

Weaning from mechanical ventilation: current controversies.

As an acute episode of respiratory failure resolves for the patient who is receiving mechanical ventilation, the sometimes difficult task of resuming spontaneous ventilation begins. The resumption of spontaneous ventilation, commonly referred to as weaning, is often difficult for the patient with preexisting lung disease. The purpose of this article is to explore the current controversies related to weaning patients from mechanical ventilation. Patients with chronic obstructive pulmonary disease are used as examples, providing the background for understanding weaning in difficult cases. Weaning is conceptualized as a process of three phases: preweaning, weaning, and extubation. Important considerations during each phase are examined.

A pilot study exploring mood state and dyspnea in mechanically ventilated patients.

OBJECTIVE: The objective of this study was to explore preweaning mood state and dyspnea in mechanically ventilated patients. METHODS: Before ventilatory weaning, 21 critically ill patients completed the short profile of mood states (higher scores equal greater disturbance), and a 10 cm dyspnea visual analogue scale (none to extremely severe). Weaning outcome at 24 hours was recorded. RESULTS: The mean +/- SD total mood disturbance (possible range, 0 to 16) and subscale scores (possible range, 0 to 4) were as follows: total, 6.10 +/- 4.06; tension, 1.07 +/- 0.64; depression, 1.16 +/- 0. 93; anger, 1.05 +/- 0.82; vigor, 1.04 +/- 0.84; fatigue, 1.96 +/- 0. 90; and confusion, 1.27 +/- 0.91. Mean dyspnea was 3.22 +/- 2.26 cm. Dyspnea intensity correlated negatively with vigor (r = -0.38, P <. 10). Lower preweaning vigor tended to differentiate successful from unsuccessful weaning (Mann-Whitney U = 22.0; P =.07). CONCLUSION: Patients who weaned successfully experienced greater mood disturbance. Moderate mood disturbance may be a necessary stimulus for successful weaning.

A guide to noninvasive intermittent ventilatory support.

Patients who use home-based medical technologies, such as noninvasive intermittent ventilatory support, may require hospitalization on units where the staff is unfamiliar with this type of equipment. Consequently, acute care clinicians need resources so they can provide safe care to these patients. This article provides background information about noninvasive intermittent ventilatory support, presents a case study to illustrate key aspects of each type of support, and provides quick reference tables to assist acute care clinicians in managing this technology.

Comparison of different methods of obtaining orthostatic vital signs.

The purpose of this study was to compare two lying and standing procedures for measuring orthostatic vital signs. Thirty-five normotensive participants (mean age 21.6 years)participated in a randomized crossover study. Measures of blood pressure (BP), heart rate, and dizziness were collected at different lying and standing times. AU subjects participated in a standardized walk paced at 4 miles per hour prior to lying. Using analysis of variance (ANOVA) with post hoc contrasts, the mean systolic BP differed between 5 and 10 minutes of lying (F = 21.33, p < .001) and the mean diastolic BP tended to differ between those time points (F = 5.23, p < .03). The mean standing systolic BP and dizziness rating were different between 0- and 2-minute intervals (F = 8.36, p < .01 and F = 7.15, p < .10). In normotensive participants following standardized exercise, orthostatic vital signs stabilized after lying 10 minutes.

A volunteers in participatory sampling survey of weaning practices. The Third National Study Group on Weaning from Mechanical Ventilation.

The survey results of the VIPs membership described in this article add qualitative information to the growing body of scientific knowledge on weaning patients off ventilators. Clearly, quantitative studies exploring the efficacy of different weaning practices across the continuum must be done if we are to accurately compare practices and prescribe the "when" and "how" of weaning. To this end, the Third National Study Group is revising the proposed weaning model and model in order to further elucidate the state of the art and science of weaning.

The art and science of caring for ventilator-assisted patients: learning from our clinical practice.

This case study describes the causes of respiratory failure, modes of ventilation, durable power of attorney, dyspnea, sedation, and chemical paralysis. Such issues as nursing interventions to care for ventilated patients, weaning from mechanical ventilation, ethical principles, and terminal weaning are also explored.

JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis.

Yes-associated protein (YAP) regulates DNA damage and chemosensitivity, as well as functioning as a pro-growth, cell size regulator. For both of its roles, regulation by phosphorylation is crucial. We undertook an in vitro screen to identify novel YAP kinases to discover new signaling pathways to better understand YAP's function. We identified JNK1 and JNK2 as robust YAP kinases, as well as mapped multiple sites of phosphorylation. Using inhibitors and siRNA, we showed that JNK specifically phosphorylates endogenous YAP in a number of cell types. We show that YAP protects keratinocytes from UV irradiation but promotes UV-induced apoptosis in a squamous cell carcinoma. We defined the mechanism for this dual role to be YAP's ability to bind and stabilize the pro-proliferative ΔNp63α isoform in a JNK-dependent manner. Our report indicates that an evaluation of the expression of the different isoforms of p63 and p73 is crucial in determining YAP's function.