Paddlebots: Translation of Rotating Colloidal Assemblies near an Air/Water Interface.

Microbot propulsion requires unique strategies due to the dominance of viscosity and the reversible nature of microscale flows. To address this, swimmers of specific structure that translate in bulk fluid are commonly used; however, another approach is to take advantage of the inherent asymmetry of liquid/solid surfaces for microbots (µbots) to walk or roll. Using this technique, we have previously demonstrated that superparamagnetic colloidal particles can be assembled into small µbots, which can quickly roll along solid surfaces. In an analogous approach, here we show that symmetry can be similarly broken near air/liquid interfaces and µbots propelled at rates comparable to those demonstrated for liquid/solid interfaces.

Multimodal microwheel swarms for targeting in three-dimensional networks.

Microscale bots intended for targeted drug delivery must move through three-dimensional (3D) environments that include bifurcations, inclined surfaces, and curvature. In previous studies, we have shown that magnetically actuated colloidal microwheels (µwheels) reversibly assembled from superparamagnetic beads can translate rapidly and be readily directed. Here we show that, at high concentrations, µwheels assemble into swarms that, depending on applied magnetic field actuation patterns, can be designed to transport cargo, climb steep inclines, spread over large areas, or provide mechanical action. We test the ability of these multimodal swarms to navigate through complex, inclined microenvironments by characterizing the translation and dispersion of individual µwheels and swarms of µwheels on steeply inclined and flat surfaces. Swarms are then studied within branching 3D vascular models with multiple turns where good targeting efficiencies are achieved over centimeter length scales. With this approach, we present a readily reconfigurable swarm platform capable of navigating through 3D microenvironments.

An experimental design for the control and assembly of magnetic microwheels.

Superparamagnetic colloidal particles can be reversibly assembled into wheel-like structures called microwheels (µwheels), which roll on surfaces due to friction and can be driven at user-controlled speeds and directions using rotating magnetic fields. Here, we describe the hardware and software to create and control the magnetic fields that assemble and direct µwheel motion and the optics to visualize them. Motivated by portability, adaptability, and low-cost, an extruded aluminum heat-dissipating frame incorporating open optics and audio speaker coils outfitted with high magnetic permeability cores was constructed. Open-source software was developed to define the magnitude, frequency, and orientation of the magnetic field, allowing for real-time joystick control of µwheels through two-dimensional (2D) and three-dimensional (3D) fluidic environments. With this combination of hardware and software, µwheels translate at speeds up to 50 µm/s through sample sizes up to 5 × 5 × 5 cm3 using 0.75 mT-2.5 mT magnetic fields with rotation frequencies of 5 Hz-40 Hz. Heat dissipation by aluminum coil clamps maintained sample temperatures within 3 °C of ambient temperature, a range conducive for biological applications. With this design, µwheels can be manipulated and imaged in 2D and 3D networks at length scales of micrometers to centimeters.

Fast In Situ Observation of Atomic Feshbach Resonances by Photoassociative Ionization.

We propose and experimentally investigate a scheme for observing Feshbach resonances in atomic quantum gases in situ and with a high temporal resolution of several tens of nanoseconds. The method is based on the detection of molecular ions, which are optically generated from atom pairs at small interatomic distances. As a test system we use a standard rubidium gas (^{87}Rb) with well known magnetically tunable Feshbach resonances. The fast speed and the high sensitivity of our detection scheme allows us to observe a complete Feshbach resonance within one millisecond and without destroying the gas.

Supersolid Properties of a Bose-Einstein Condensate in a Ring Resonator.

We investigate the dynamics of a Bose-Einstein condensate interacting with two noninterfering and counterpropagating modes of a ring resonator. Superfluid, supersolid, and dynamic phases are identified experimentally and theoretically. The supersolid phase is obtained for sufficiently equal pump strengths for the two modes. In this regime we observe the emergence of a steady state with crystalline order, which spontaneously breaks the continuous translational symmetry of the system. The supersolidity of this state is demonstrated by the conservation of global phase coherence at the superfluid to supersolid phase transition. Above a critical pump asymmetry the system evolves into a dynamic runaway instability commonly known as collective atomic recoil lasing. We present a phase diagram and characterize the individual phases by comparing theoretical predictions with experimental observations.

Three-dimensional docking of alcohols to ketones: an experimental benchmark based on acetophenone solvation energy balances.

The two hydrogen bond solvation sites exhibited by the carbonyl group in acetophenone are influenced by alkylation of the methyl group in both the acetophenone and in the prototype solvent methanol, largely due to London dispersion forces. Phenyl docking and alkyl docking preferences can be realized at will by appropriate substitution. In particular, cyclopropylation helps to stabilize the opposite phenyl docking site. In all cases, the energy gap is small enough to allow for a simultaneous detection even under low temperature conditions. This density functional prediction is checked experimentally by jet FTIR spectroscopy and largely confirmed. A spurious out-of-plane solvation preference predicted for cyclopropylphenylketone with tert-butyl alcohol by B3LYP-D3 calculations is not confirmed experimentally. It is unlikely that this discrepancy is due to zero-point energy effects. Instead, the second most stable alkyl-side solvation motif predicted with a more in-plane coordination is found in the jet expansion. Overall, the ability of carbonyl solvation balances to benchmark subtle electronic structure effects for non-covalent interactions without major nuclear motion corrections is supported.

Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6-deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

Single versus repeated exposure to human polarized intestinal epithelial monolayers for in vitro protein hazard characterization.

Recent studies suggest human-derived intestinal epithelial cell (IEC) lines cultured as polarized monolayers on permeable Transwell® filters are effective at differentiating between hazardous and non-hazardous proteins following a single exposure. In this study, IEC polarized monolayers were subjected to hazardous or non-hazardous proteins in nine exposures over 30 days and compared to a single exposure of the same protein. The objective was to evaluate whether repeated exposures to a protein differently alter barrier integrity or compromise cell viability compared to single exposures. Proteins tested included Clostridium difficile toxin A, Streptolysin O, Wheat Germ Agglutinin, Phaseolus vulgaris Hemagglutinin-E, bovine serum albumin, porcine serum albumin, and fibronectin. Evidence of diminished barrier integrity and/or cell viability following exposure to hazardous proteins was more pronounced in magnitude when IECs were subjected to multiple rather than single exposures. In some cases, an effect on IEC monolayers was observed only with repeated exposures. In general, IEC responses to non-hazardous proteins following either single or repeated exposures were minimal. Results from these studies support the utility of using cultured human IEC polarized monolayers to differentiate between hazardous and non-hazardous proteins and suggest that repeated exposures may reveal a greater magnitude of response when compared to single exposures.

Framing of the opioid problem in cancer pain management in Canada.

Two guidelines about opioid use in chronic pain management were published in 2017: the Canadian Guideline for Opioids for Chronic Non-Cancer Pain and the European Pain Federation position paper on appropriate opioid use in chronic pain management. Though the target populations for the guidelines are the same, their recommendations differ depending on their purpose. The intent of the Canadian guideline is to reduce the incidence of serious adverse effects. Its goal was therefore to set limits on the use of opioids. In contrast, the European Pain Federation position paper is meant to promote safe and appropriate opioid use for chronic pain. The content of the two guidelines could have unintentional consequences on other populations that receive opioid therapy for symptom management, such as patients with cancer. In this article, we present expert opinion about those chronic pain management guidelines and their impact on patients with cancer diagnoses, especially those with histories of substance use disorder and psychiatric conditions. Though some principles of chronic pain management can be extrapolated, we recommend that guidelines for cancer pain management should be developed using empirical data primarily from patients with cancer who are receiving opioid therapy.

Attachment security and existential distress among patients with advanced cancer.

BACKGROUND: Felt security in close relationships may affect individual adaptation responses to existential threat in severe illness. We examined the contribution of attachment security to demoralization, a state of existential distress involving perceived pointlessness and meaninglessness in advanced cancer. METHOD: A mixed cross-sectional sample of 382 patients with advanced cancer (mean age 59, 60% female) was recruited from outpatient oncology clinics. Participants completed self-report measures of attachment security, demoralization, depression, and physical symptom burden. We used multiple linear regression to analyze the association between attachment security and demoralization, controlling for demographic factors and symptom burden and tested whether attachment security moderated the association of symptom burden with demoralization. Separate analyses compared the contribution of the dimensions of attachment anxiety and attachment avoidance. RESULTS: The prevalence of clinically relevant demoralization was 35%. Demoralization was associated with lower attachment security (ß = -0.54, 95%CI: -0.62 to 0.46). This effect was empirically stronger for attachment anxiety (ß = 0.52, 95%CI: 0.44 to 0.60) compared to attachment avoidance (ß = 0.36, 95%CI: 0.27 to 0.45). Attachment security also significantly moderated the association of physical symptom burden with demoralization, such that with less attachment security, there was a stronger association between symptom burden and demoralization. CONCLUSION: Attachment security may protect from demoralization in advanced cancer. Its relative lack, particularly on the dimension of attachment anxiety, may limit adaptive capacities to deal with illness burden and to sustain morale and purpose in life. An understanding of individual differences in attachment needs can inform existential interventions for severely ill individuals.

Pinning Transition of Bose-Einstein Condensates in Optical Ring Resonators.

We experimentally investigate the dynamic instability of Bose-Einstein condensates in an optical ring resonator that is asymmetrically pumped in both directions. We find that, beyond a critical resonator-pump detuning, the system becomes stable regardless of the pump strength. Phase diagrams and quenching curves are presented and described by numerical simulations. We discuss a physical explanation based on a geometric interpretation of the underlying nonlinear equations of motion.

Observation of Subradiant Atomic Momentum States with Bose-Einstein Condensates in a Recoil Resolving Optical Ring Resonator.

We experimentally investigate the formation of subradiant atomic momentum states in Bose-Einstein condensates inside a recoil resolving optical ring resonator according to the theoretical proposal of Cola, Bigerni, and Piovella. The atoms are pumped from the side with laser light that contains two frequency components. They resonantly drive cavity assisted Raman transitions between three discreet atomic momentum states. Within a few hundred microseconds, the system evolves into a stationary subradiant state. In this state, the condensate develops two density gratings suitable to diffract the two frequency components of the pump field into the resonator. Both components destructively interfere such that scattering is efficiently suppressed. A series of subradiant states for various amplitude ratios of the two pump components between 0 and 2.1 have been observed. The results are well explained with a three state quantum model in mean field approximation.

Extended exposure duration of cultured intestinal epithelial cell monolayers in characterizing hazardous and non-hazardous proteins.

Recent studies suggest that human derived intestinal epithelial cells (IECs) cultured as polarized monolayers on Transwell® filters may respond differently when exposed to hazardous and non-hazardous proteins. This experimental platform was based on apical exposure of IEC monolayers to test proteins for 24 h followed by assessment of barrier integrity and cell viability. In this study, Caco-2 and T84 IEC polarized monolayers were evaluated for barrier integrity and cytotoxicity following exposure to hazardous and non-hazardous proteins for 24, 48 and 72 h. Hazardous proteins included Clostridium difficile toxin A (ToxA), Streptolysin O (SLO), Wheat Germ Agglutinin (WGA), and Phaseolus vulgaris haemagglutinin-E (PHA-E). Non-hazardous proteins included bovine serum albumin (BSA), porcine serum albumin (PSA), and fibronectin (Fbn). In general, evidence of diminished barrier integrity or cell viability observed following exposure to hazardous proteins for 24 h was more pronounced after 48 and 72 h for both IEC monolayers. Non-hazardous proteins exhibiting no impact following 24 h of exposure elicited minimal effects over longer exposure durations. These results support the utility of using cultured human IEC polarized monolayers to differentiate between hazardous and non-hazardous proteins and suggest that longer durations of exposure may further improve the ability to distinguish between them.

Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein.

An experimental platform employing human derived intestinal epithelial cell (IEC) line monolayers grown on permeable Transwell® filters was previously investigated to differentiate between hazardous and innocuous proteins. This approach was effective at distinguishing these types of proteins and perturbation of monolayer integrity, particularly transepithelial electrical resistance (TEER), was the most sensitive indicator. In the current report, in vitro indicators of monolayer integrity, cytotoxicity, and inflammation were evaluated using primary (non-transformed) human polarized small intestinal epithelial barriers cultured on Transwell® filters to compare effects of a hazardous protein (Clostridium difficile Toxin A [ToxA]) and an innocuous protein (bovine serum albumin [BSA]). ToxA exerted a reproducible decrease on barrier integrity at doses comparable to those producing effects observed from cell line-derived IEC monolayers, with TEER being the most sensitive indicator. In contrast, BSA, tested at concentrations substantially higher than ToxA, did not cause changes in any of the tested variables. These results demonstrate a similarity in response to certain proteins between cell line-derived polarized IEC models and a primary human polarized small intestinal epithelial barrier model, thereby reinforcing the potential usefulness of cell line-derived polarized IECs as a valid experimental platform to differentiate between hazardous and non-hazardous proteins.

Preliminary psychometrics of the Existential Distress Scale in patients with advanced cancer.

Existential distress is of clinical concern in patients with terminal illness. Although existential distress has been used to describe a broad spectrum of psychological disturbances, its narrower definition may be confined to distress that arises when the meaning and value of one's life is unclear, and is comorbid with feelings of loneliness and low self-worth. To promote further study, we developed and pilot-tested a 10-item Existential Distress Scale (EDS). Twenty-one patients with advanced cancer were recruited from a palliative care unit. Measures of existential distress, death anxiety, depression, performance status and physical symptom burden were collected. The EDS showed promising psychometric properties, including significant associations with death anxiety and depression. Thirty-eight per cent of the sample reported great or unbearable distress on at least one existential concern. The EDS may be administered to measure existential distress in patients with advanced cancer and clinicians may find the instrument useful to initiate a structured discussion about this symptom.

Impact of early palliative care on caregivers of patients with advanced cancer: cluster randomised trial.

Background: Early palliative care improves the quality of life (QoL) and satisfaction with care of patients with advanced cancer, but little is known about its effect on caregivers. Here, we report outcomes of caregiver satisfaction with care and QoL from a trial of early palliative care. Patients and methods: Twenty-four medical oncology clinics were cluster-randomised, stratified by tumour site (lung, gastrointestinal, genitourinary, breast and gynaecological), to early palliative care team referral, or to standard oncology care with palliative care only as needed. Caregivers of patients with advanced cancer (clinical prognosis of 6-24 months, Eastern Cooperative Oncology Group 0-2) in both trial arms completed validated measures assessing satisfaction with care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)], at baseline and monthly for 4 months. We used a multilevel linear random-intercept mixed-effect model to test whether there was improvement in the intervention group relative to the control group over 3 and 4 months. Results: A total of 182 caregivers completed baseline measures (94 intervention, 88 control); 151 caregivers (77 intervention, 74 control) completed at least one follow-up assessment. Satisfaction with care improved in the palliative intervention group compared with controls over 3 months (P = 0.007) and 4 months (P = 0.02). There was no significant improvement in the intervention group compared with controls for CQoL-C (3 months: P = 0.92, 4 months: P = 0.51), Physical Component Summary of the SF-36v2 Health Survey (3 months: P = 0.83, 4 months: P = 0.20), or Mental Component Summary of the SF-36v2 Health Survey (3 months: P = 0.87, 4 months: P = 0.60). Conclusion: Early palliative care increased satisfaction with care in caregivers of patients with advanced cancer. ClinicalTrials.gov identifier: NCT01248624.

Canadian recommendations for the management of breakthrough cancer pain.

Breakthrough cancer pain (btcp) represents an important element in the spectrum of cancer pain management. Because most btcp episodes peak in intensity within a few minutes, speed of medication onset is crucial for proper control. In Canada, several current provincial guidelines for the management of cancer pain include a brief discussion about the treatment of btcp; however, there are no uniform national recommendations for the management of btcp. That lack, accompanied by unequal access to pain medication across the country, contributes to both regional and provincial variability in the management of btcp. Currently, immediate-release oral opioids are the treatment of choice for btcp. This approach might not always offer optimal speed for onset of action and duration to match the rapid nature of an episode of btcp. Novel transmucosal fentanyl formulations might be more appropriate for some types of btcp, but limited access to such drugs hinders their use. In addition, the recognition of btcp and its proper assessment, which are crucial steps toward appropriate treatment selection, remain challenging for many health care professionals. To facilitate appropriate management of btcp, a group of prominent Canadian specialists in palliative care, oncology, and anesthesiology convened to develop a set of recommendations and suggestions to assist Canadian health care providers in the treatment of btcp and the alleviation of the suffering and discomfort experienced by adult cancer patients.

[Adequate fluid resuscitation in septic shock with high catecholamine doses]. / Adäquate Volumensubstitution bei septischem Schock unter hohen Katecholamindosen.

BACKGROUND: Appropriate fluid resuscitation is a fundamental aspect for the hemodynamic management of septic shock patients and should ideally be achieved before vasopressors and positive inotropic substances are administered. The development of hemodynamic monitoring has revealed that in some cases patients had been improperly treated with high-dose catecholamines for initially insufficient fluid resuscitation. The aim of this study was to show that in some cases it is possible to actively reduce catecholamines by a volume challenge adapted according to the individual patient needs. MATERIAL AND METHODS: In this retrospective observational study 29 patients with septic shock in a surgical intensive care unit (ICU) at a university hospital (17 male, 12 female, mean age 71 ± 10 years) on high-dose catecholamines (median values norepinephrine 0.204 µg/kg body weight/min, dobutamine 3.876 µg/kg/min and epinephrine 0.025 µg/kg/min, ranging up to 0.810 µg/kg/min, 22.222 µg/kg/min and 0.407 µg/kg/min in 28, 20 and 17 patients, respectively) were analyzed. The extremities of the patients were initially cold with a mottled marbled appearance whereas the mean arterial pressure (MAP) was ≥ 65 mmHg. The median central venous pressure (CVP) was 17 mmHg (range 55-34 mmHg) and the mean lactate concentration was 2.78 mmol/l (range 0.93-10.67 mmol/l). The standard therapy concept consisted of a forced volume challenge combined with active reduction of catecholamines to achieve an adequate fluid loading status, guided by the passive leg raising test (PLR), clinical signs and in 19 cases by hemodynamic monitoring (pulmonary artery catheter Vigilance II(™) n = 10, FloTrac(™), Vigileo(™) n = 9 and PreSep(™) n = 5; Edwards Life Sciences). The forced volume challenge was stopped after clinical improvement with rewarmed extremities, increasing diuresis volumes and lack of improvement by PLR. RESULTS: Catecholamine doses could be significantly reduced in all patients: norepinephrine to 0 µg/kg/min, dobutamine to 1.852 µg/kg/min and epinephrine to 0 µg/kg/min (up to 0.133 µg/kg/min, 6.289 µg/kg/min and 0.091 µg/kg/min, respectively, p < 0.05 Wilcoxon signed rank test). Volume challenge test: + 4,500 ml Ringer solution (range 0-24,000 ml) and 1,000 ml hydroxyethyl starch (range 0-2,500 ml) and mean fluid balance + 6,465 ml (range + 2,040 ml to + 27,255 ml). The median weaning time from catecholamines was 12 h (range 4-43 h). After treatment all patients showed rewarmed extremities and a decrease in mean lactate levels from 2.78 mmol/l (range 0.93-10.67 mmol/l) to 2.05 mmol/l (range 0.7-5.4 mmol/l). The measured hemodynamic constellations showed clear interindividual differences but no cardiac deterioration occurred. The median oxygenation index (paO2/FiO2) showed a statistically insignificant change from 264 mmHg (range 75-418 mmHg) to 250 mmHg (range 120-467 mmHg). Of the patients 20 survived and 9 died. CONCLUSION: It is possible to wean a substantial proportion of septic shock patients from high-dose catecholamines in combination with a needs-adapted forced volume challenge test. The importance of appropriate fluid loading prior to the use of high catecholamine doses should be a main subject of discussion in patients with severe septic shock and was confirmed in this study. This should be oriented to clinical and if possible, hemodynamic parameters and should not be underestimated.