Frequency-Domain Low-Wavenumber Hyperspectral Stimulated Raman Scattering Microscopy.

In recent years, stimulated Raman scattering (SRS) microscopy has experienced rapid technological advancements and has found widespread applications in chemical analysis. Hyperspectral SRS (hSRS) microscopy further enhances the chemical selectivity in imaging by providing a Raman spectrum for each pixel. Time-domain hSRS techniques often require interferometry and ultrashort femtosecond laser pulses. They are especially suited to measuring low-wavenumber Raman transitions but are susceptible to scattering-induced distortions. Frequency-domain hSRS microscopy, on the other hand, offers a simpler optical configuration and demonstrates high tolerance to sample scattering but typically operates within the spectral range of 400-4000 cm-1. Conventional frequency-domain hSRS microscopy is widely employed in biological applications but falls short in detecting chemical bonds with a weaker vibrational energy. In this work, we extend the spectral coverage of picosecond spectral-focusing hSRS microscopy to below 100 cm-1. This frequency-domain low-wavenumber hSRS approach can measure the weaker vibrational energy from the sample and has a strong tolerance to sample scattering. By expanding spectral coverage to 100-4000 cm-1, this development enhances the capability of spectral-domain SRS microscopy for chemical imaging.

Are investigators' access to trial data and rights to publish restricted and are potential trial participants informed about this? A comparison of trial protocols and informed consent materials.

OBJECTIVES: To determine to which degree industry partners in randomised clinical trials own the data and can constrain publication rights of academic investigators. METHODS: Cohort study of trial protocols, publication agreements and other documents obtained through Freedom of Information requests, for a sample of 42 trials with industry involvement approved by ethics committees in Denmark. The main outcome measures used were: proportion of trials where data was owned by the industry partner, where the investigators right to publish were constrained and if this was mentioned in informed consent documents, and where the industry partner could review data while the trial was ongoing and stop the trial early. RESULTS: The industry partner owned all data in 20 trials (48%) and in 16 trials (38%) it was unclear. Publication constraints were described for 30 trials (71%) and this was not communicated to trial participants in informed consent documents in any of the trials. In eight trials (19%) the industry partner could review data during the trial, for 20 trials (48%) it was unclear. The industry partner could stop the trial early without any specific reason in 23 trials (55%). CONCLUSIONS: Publication constraints are common, and data is often owned by industry partners. This is rarely communicated to trial participants. Such constraints might contribute to problems with selective outcome reporting. Patients should be fully informed about these aspects of trial conduct.

Poor Sleep and Its Relation to Impulsivity in Patients with Antisocial or Borderline Personality Disorders.

Studies investigating sleep and personality disorders consistently demonstrate a relation between personality disorders characterized by behavioral disinhibition and/or emotional dysregulation (traditionally termed cluster B personality disorders) and poor sleep. This finding is in line with previous studies associating insomnia with impulsive behavior, since this is a core characteristic of both antisocial and borderline personality disorder. The current study investigates a group (n = 112) of forensic psychiatric inpatients with antisocial or borderline personality disorder or traits thereof. Subjective sleep characteristics and impulsivity were assessed with the Pittsburgh Sleep Quality Index, the Sleep Diagnosis List, and the Barratt Impulsiveness Scale, respectively. More than half of the patients (53.6%) report poor sleep quality and 22.3% appears to suffer from severe chronic insomnia. Both poor sleep quality and chronic insomnia are significantly associated with self-reported impulsivity, in particular with attentional impulsiveness. This association was not significantly influenced by comorbid disorders. Actively treating sleep problems in these patients may not only improve sleep quality, mental health, and physical well-being, but may also have impact on impulsivity-related health risks by increasing self-control.

Positive end-expiratory pressure titration at bedside using electrical impedance tomography in post-operative cardiac surgery patients.

BACKGROUND: Post-operative positive end-expiratory pressure (PEEP) setting to minimize the risk of ventilator-associated lung injury is still controversial. Assessment of regional ventilation distribution by electrical impedance tomography (EIT) might be superior as compared with global parameters. The aim of this prospective observational study was to compare global dynamic compliance (CRS ) with different EIT indices during a short clinical applicable descending PEEP trial. METHODS: Twenty mechanically ventilated patients after elective cardiac surgery received a standard recruitment manoeuvre (RM) following descending PEEP trial in steps of 2 cmH2 O from PEEP 14 cmH2 O to 6 cmH2 O. During baseline and all PEEP steps, CRS was assessed and regional ventilation distribution was measured by means of EIT. The individual 'best' PEEP values for the derived EIT indices and CRS were calculated and compared. RESULTS: The descending PEEP trial lasted less than 10 min. CRS increased after the RM and showed a maximum value at PEEP 8 cmH2 O. Ventilation distribution shifted more to dependent lung regions after RM and back to more non-dependent regions during the PEEP trial. Individual 'best' PEEP by CRS showed significantly lower values than 'best' PEEP by ventilation distribution measured with EIT indices. CONCLUSION: During a short descending PEEP trial at bedside, EIT is capable of following the status of regional ventilation distribution in ventilated patients. The 'best' PEEP value identified by individual maximum CRS was lower than optimal PEEP levels as determined by means of EIT indices. EIT could help setting PEEP in post-operative ventilated patients.

Spatiotemporally Precise Optical Manipulation of Intracellular Molecular Activities.

Controlling chemical processes in live cells is a challenging task. The spatial heterogeneity of biochemical reactions in cells is often overlooked by conventional means of incubating cells with desired chemicals. A comprehensive understanding of spatially diverse biochemical processes requires precise control over molecular activities at the subcellular level. Herein, a closed-loop optoelectronic control system is developed that allows the manipulation of biomolecular activities in live cells at high spatiotemporal precision. Chemical-selective fluorescence signals are utilized to command lasers that trigger specific chemical processes or control the activation of photoswitchable inhibitors at desired targets. This technology is fully compatible with laser scanning confocal fluorescence microscopes. The authors demonstrate selective interactions of a 405 nm laser with targeted organelles and simultaneous monitoring of cell responses by fluorescent protein signals. Notably, blue laser interaction with the endoplasmic reticulum leads to a more pronounced reduction in cytosolic green fluorescent protein signals in comparison to that with nuclei and lipid droplets. Moreover, when combined with a photoswitchable inhibitor, microtubule polymerization is selectively inhibited within the subcellular compartments. This technology enables subcellular spatiotemporal optical manipulation over chemical processes and drug activities, exclusively at desired targets, while minimizing undesired effects on non-targeted locations.

AARC Clinical Practice Guideline: Spontaneous Breathing Trials for Liberation From Adult Mechanical Ventilation.

Despite prior publications of clinical practice guidelines related to ventilator liberation, some questions remain unanswered. Many of these questions relate to the details of bedside implementation. We, therefore, formed a guidelines committee of individuals with experience and knowledge of ventilator liberation as well as a medical librarian. Using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we make the following recommendations: (1) We suggest that calculation of a rapid shallow breathing index is not needed to determine readiness for a spontaneous breathing trial (SBT) (conditional recommendation; moderate certainty); (2) We suggest that SBTs can be conducted with or without pressure support ventilation (conditional recommendation, moderate certainty); (3) We suggest a standardized approach to assessment and, if appropriate, completion of an SBT before noon each day (conditional recommendation, very low certainty); and (4) We suggest that FIO2 should not be increased during an SBT (conditional recommendation, very low certainty). These recommendations are intended to assist bedside clinicians to liberate adult critically ill patients more rapidly from mechanical ventilation.

2022 Year in Review: Ventilator Liberation.

Mechanical ventilation is ubiquitous in critical care, and duration of ventilator liberation is variable and multifactorial. While ICU survival has increased over the last two decades, positive-pressure ventilation can cause harm to patients. Weaning and discontinuation of ventilatory support is the first step in ventilator liberation. Clinicians have a wealth of evidence-based literature at their disposal; however, more high-quality research is needed to describe outcomes. Additionally, this knowledge must be distilled into evidence-based practice and applied at the bedside. A proliferation of research on the subject of ventilator liberation has been published in the last 12 months. Whereas some authors have reconsidered the value of applying the rapid shallow breathing index in weaning protocols, others have begun to investigate new indices to predict liberation outcomes. New tools such as diaphragmatic ultrasonography have begun to appear in the literature as a tool for outcome prediction. A number of systematic reviews with both meta-analysis and network meta-analysis that synthesize the literature on ventilator liberation have also been published in the last year. This review describes changes in performance, monitoring of spontaneous breathing trials, and evaluations of successful ventilator liberation.

Chemical-imaging-guided optical manipulation of biomolecules.

Chemical imaging via advanced optical microscopy technologies has revealed remarkable details of biomolecules in living specimens. However, the ways to control chemical processes in biological samples remain preliminary. The lack of appropriate methods to spatially regulate chemical reactions in live cells in real-time prevents investigation of site-specific molecular behaviors and biological functions. Chemical- and site-specific control of biomolecules requires the detection of chemicals with high specificity and spatially precise modulation of chemical reactions. Laser-scanning optical microscopes offer great platforms for high-speed chemical detection. A closed-loop feedback control system, when paired with a laser scanning microscope, allows real-time precision opto-control (RPOC) of chemical processes for dynamic molecular targets in live cells. In this perspective, we briefly review recent advancements in chemical imaging based on laser scanning microscopy, summarize methods developed for precise optical manipulation, and highlight a recently developed RPOC technology. Furthermore, we discuss future directions of precision opto-control of biomolecules.

Characteristics, Identification, Training, and Perception of Leaders in Respiratory Care.

BACKGROUND: Leadership is critical to high-functioning teams; however, data are lacking for what defines successful respiratory therapist (RT) leadership. Leaders need a wide range of skills to be successful, although the exact characteristics, behaviors, and accomplishments of successful RT leaders are unknown. We performed a survey of respiratory care leaders to evaluate different aspects of RT leadership. METHODS: We developed a survey of RT leaders to examine respiratory care leadership in a variety of professional settings. Different aspects of leadership and the relationships between perceptions of leadership and well-being were assessed. Data analysis was descriptive. RESULTS: We received 124 responses, with a response rate of 37%. Respondents had a median 22 y of RT experience, and 69% were in leadership positions. The most-important skills identified for potential leaders were critical thinking (90%) and people skills (88%). Self-initiated projects (82%), intradepartmental education (71%), and precepting (63%) were noted accomplishments. Reasons for exclusion from leadership included poor work ethic (94%), dishonesty (92%), difficulty getting along with others (89%), unreliable (90%), and not being a team player (86%). Most respondents (77%) agreed American Association for Respiratory Care membership be a requirement for leadership; however, 31% required membership. Integrity (71%) was noted consistently as a characteristic of successful leaders. There was no consensus for behaviors of successful versus unsuccessful leaders or what defines successful leadership. Ninety-five percent of leaders had received some leadership training. Respondents reported that well-being is affected by leadership, departmental culture, peers, and leaders with burnout; 34% of respondents felt people with burnout received good support at their institution, whereas 61% felt maintaining well-being is left to individuals. CONCLUSIONS: Critical thinking and people skills were the most-important skills for potential leaders. Limited consensus existed on characteristics, behaviors, and defined success of leaders. Most respondents agreed leadership influences well-being.

Enhancing Respiratory Therapists' Well-Being: Battling Burnout in Respiratory Care.

Burnout is a major problem in health care and is associated with adverse sequelae for patients, health care workers, and organizations. Burnout among respiratory therapists (RTs) is as high as 79% and is associated with poor or ineffective leadership, inadequate staffing, high work load, non-leadership position, and work environment. An understanding of burnout is necessary for both staff and leadership to ensure RT well-being. This narrative review will discuss the psychology of burnout, prevalence, drivers, mitigation strategies, and future directions for research.

Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5.

Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and cancers. We report an improved carba-NAD synthesis, including a pyrophosphate coupling method that proceeds in approximately 60% yield. We also disclose the X-ray crystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-NAD. These X-ray crystal structures provide critical snapshots of the mechanism by which human sirtuins function as protein deacylation catalysts.

AARC Clinical Practice Guideline: Management of Adult Patients With Oxygen in the Acute Care Setting.

Providing supplemental oxygen to hospitalized adults is a frequent practice and can be administered via a variety of devices. Oxygen therapy has evolved over the years, and clinicians should follow evidence-based practices to provide maximum benefit and avoid harm. This systematic review and subsequent clinical practice guidelines were developed to answer questions about oxygenation targets, monitoring, early initiation of high-flow oxygen (HFO), benefits of HFO compared to conventional oxygen therapy, and humidification of supplemental oxygen. Using a modification of the RAND/UCLA Appropriateness Method, 7 recommendations were developed to guide the delivery of supplemental oxygen to hospitalized adults: (1) aim for [Formula: see text] range of 94-98% for most hospitalized patients (88-92% for those with COPD), (2) the same [Formula: see text] range of 94-98% for critically ill patients, (3) promote early initiation of HFO, (4) consider HFO to avoid escalation to noninvasive ventilation, (5) consider HFO immediately postextubation to avoid re-intubation, (6) either HFO or conventional oxygen therapy may be used with patients who are immunocompromised, and (7) consider humidification for supplemental oxygen when flows > 4 L/min are used.

Improving Students' Knowledge and Skills Through a Tele-ICU Clinical Rotation.

BACKGROUND: In the course of their education, respiratory therapy students participate in clinical rotations, which are essential to their education. Recently, the number of clinical sites has decreased as some have been eliminated. During the COVID-19 pandemic, schools were challenged to find hospitals to accommodate students due to the risk of infection. Tele-ICU has emerged as a means for staff therapists to assess and monitor patients via remote monitoring systems. We hypothesized that a clinical rotation at a tele-ICU would strengthen students' knowledge of mechanical ventilation, telemedicine, and COVID-19. METHODS: In this study, students completed clinical rotations in a tele-ICU. Students spent two 4-h clinical rotations rounding on 320 ICU beds at 5 hospitals. Under the supervision of experienced therapists, students performed remote patient-ventilator assessments, including review and interpretation of ventilator waveforms, patient-ventilator interaction, arterial blood gases, and chest x-rays. Students completed pre- and post-rotation surveys assessing their confidence managing mechanical ventilation, experience with telemedicine, ARDS, and patients with COVID-19. RESULTS: Mean self-confidence in mechanical ventilation (P = .001), assessing waveforms (P = .001), and knowledge of ARDS increased after the clinical rotation (P = .001). Similarly, reported knowledge related to spontaneous breathing trial protocols (P = .009), lung-protective ventilation (P = .002), patient care planning (P = .001), and use of Excel spreadsheets (P = .002) increased from the beginning to the end of the clinical rotation. Student confidence in interprofessional communication increased from 85 [69-98] to 95 [78-100]; P = .03). Overall, the largest change was students' ability to assess patients with COVID-19 (pre-rotation 50.0 [11.5-65.7], post-rotation 80.0 [58.5-100]; P = .001). Qualitative results revealed overwhelmingly positive results for both students and preceptors. CONCLUSIONS: Students' confidence in assessing patients via remote monitoring increased in a tele-ICU clinical rotation. Self-assessed knowledge related to COVID-19 also increased to statistical significance.

Well-Being Among Respiratory Therapists in an Academic Medical Center During the COVID-19 Pandemic.

BACKGROUND: Recent studies have revealed high rates of burnout among respiratory therapists (RTs), which has implications for patient care and outcomes as well as for the health care workforce. We sought to better understand RT well-being during the COVID-19 pandemic. The purpose of this study was to determine rates and identify determinants of well-being, including burnout and professional fulfillment, among RTs in ICUs. METHODS: We conducted a mixed-methods study comprised of a survey administered quarterly from July 2020-May 2021 to critical-care health care professionals and semi-structured interviews from April-May 2021 with 10 ICU RTs within a single health center. We performed multivariable analyses to compare RT well-being to other professional groups and to evaluate changes in well-being over time. We analyzed qualitative interview data using thematic analysis, followed by mapping themes to the Maslow needs hierarchy. RESULTS: One hundred eight RTs responded to at least one quarterly survey. Eighty-two (75%) experienced burnout; 39 (36%) experienced professional fulfillment, and 62 (58%) reported symptoms of depression. Compared to clinicians of other professions in multivariable analyses, RTs were significantly more likely to experience burnout (odds ratio 2.32 [95% CI 1.41-3.81]) and depression (odds ratio 2.73 [95% CI 1.65-4.51]) and less likely to experience fulfillment (odds ratio 0.51 [95% CI 0.31-0.85]). We found that staffing challenges, safety concerns, workplace conflict, and lack of work-life balance led to burnout. Patient care, use of specialized skills, appreciation and a sense of community at work, and purpose fostered professional fulfillment. Themes identified were mapped to Maslow's hierarchy of needs; met needs led to professional fulfillment, and unmet needs led to burnout. CONCLUSIONS: ICU RTs experienced burnout during the pandemic at rates higher than other professions. To address RT needs, institutions should design and implement strategies to reduce burnout across all levels.