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The use of noninvasive ventilation (NIV) has dramatically increased over the last decade. This increase is multifaceted with regard to the number of patients receiving NIV and in the increasingly varied disease conditions for which NIV is being used. Successful development of an NIV program depends on many variables, but perhaps most important is a multidisciplinary approach that incorporates experience and education. Many aspects of an NIV program must come together to make it successful for both patients and clinicians. Among these are needs assessment, institutional buy-in, use of proper equipment, staff and patient training, protocols/guidelines, and outcomes. We analyze these issues and identify characteristics that produce a successful NIV program. [ABSTRACT FROM AUTHOR]

Soon after diagnosis with type 1 diabetes (T1D), many patients experience a period of partial remission. A longer partial remission is associated with a better response to treatment, but the mechanism is not known. The frequency of CD4 + CD25 + CD127 hi (127-hi) cells, a cell subset with an anti-inflammatory Th2 bias, correlates positively with length of partial remission. The purpose of this study was to further characterize the nature of the Th2 bias in 127-hi cells. Single cell RNA sequencing paired with TCR sequencing of sorted 127-hi memory cells identifies clonally expanded Th2 clusters in 127-hi cells from T1D, but not from healthy donors. The Th2 clusters express GATA3, GATA3-AS1, PTGDR2, IL17RB, IL4R and IL9R. The existence of 127-hi Th2 cell clonal expansion in T1D suggests that disease factors may induce clonal expansion of 127-hi Th2 cells that prolong partial remission and delay disease progression., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

For over 10 years, several bolometer sensors with different properties have been tested in the IBOVAC facility. The aim has been to develop a bolometer sensor that can be operated in ITER and can withstand harsh operating conditions. For this purpose, important physical properties of the sensors, i.e., cooling time constant τ, normalized heat capacity κ, and normalized sensitivity s n , have been characterized in a vacuum condition and at various temperatures up to 300 °C. The calibration is achieved by ohmic heating of the sensor absorbers by applying a DC voltage and recording exponential current fall during heating. Recently, a Python program was developed to analyze the data and extract the above mentioned parameters including the uncertainties from recorded currents. In the present series of experiments, the latest prototype sensors developed for ITER are tested and evaluated. These include three different sensor types: two with Au absorbers on ZrO 2 membranes (self-supporting substrate sensors) and one with Au absorbers on Si 3 N 4 membranes supported by a Si frame (supported membrane sensors). Tests revealed that the sensor with ZrO 2 substrate can only be operated up to 150 °C, while the supported membrane sensors passed the tests up to 300 °C successfully. These results will be used, together with other upcoming tests, such as irradiation testing, to select the most suitable sensors to be employed in ITER.

Objective: This study assesses how the volume of pancreatic-adjacent operations (PAO) impacts the outcomes of pancreaticoduodenectomy (PD)., Summary Background Data: It is well-established that regionalization benefits outcomes after PD. However, due to a multitude of factors, including geographic, financial, and personal, not all patients receive their care at high-volume pancreas surgery centers., Methods: The National Cancer Database was queried for pancreatic cancer patients who underwent PD. Hospital volume was calculated for PD and PAO (defined as gastric, hepatic, complex biliary, or pancreatic operations other than PD) and dichotomized as low- and high-volume centers based on the median. Three study cohorts were created: low-volume hospitals (LVH) for both PD and PAO, mixed-volume hospital (MVH) with low-volume PD but high-volume PAO, and high-volume PD hospital (HVH)., Results: In total, 24,572 patients were identified, with 41.5%, 7.2%, and 51.3% patients treated at LVH, MVH, and HVH, respectively. Thirty-day mortality for PD was 5.6% in LVH, 3.2% in MVH, and 2.5% in HVH. On multivariable analyses, LVH was predictive for higher 30-day mortality compared to HVH [odds ratio (OR) 2.068; 95% confidence interval (CI) 1.770-2.418; P< 0.0001]. However, patients at MVH demonstrated similar 30-day mortality to patients treated at HVH (OR 1.258; 95% CI 0.942-1.680; P = 0.1203)., Conclusions: PD outcomes at low-volume centers that have experience with complex cancer operations near the pancreas are similar to PD outcomes at hospitals with high PD volume. MVH provides a model for PD outcomes to improve quality and access for patients who cannot, or choose not to, receive their care at high-volume centers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Accumulation of secretions in an endotracheal tube can increase the resistance to flow resulting in an increased patient work of breathing when the patient is interacting with the ventilator. Retained secretions can also serve as an infection risk. Standard suction catheters are limited in their ability to keep the lumen of the endotracheal tube clear. A novel closed-suction catheter has been introduced that incorporates a balloon at its distal end that, when inflated, physically scrapes secretions out of the endotracheal tube (CleanSweep catheter (CSC), Teleflex, Morrisville NC). We hypothesized that the CSC would be more efficient at removing secretions from inside the endotracheal tube than a standard suction catheter (SSC)., Methods: We performed a bench study examining resistive pressures across different sizes of endotracheal tubes when cleaned by the CSC as compared with an SSC. This study was followed by a prospective crossover study again comparing the CSC with an SSC in intubated intensive care unit patients receiving mechanical ventilation and requiring frequent suctioning., Results: For the bench study the CSC was significantly better in reducing airway resistive pressures ( P < 0.001). In the prospective crossover study the CSC over 2 h also removed significantly more secretions than the SSC ( P < 0.05)., Conclusion: Both our bench and crossover clinical study demonstrated improved clearance of secretions with the CSC vs an SSC. Further research is needed to ascertain the clinical outcome benefits of enhanced secretion removal., Competing Interests: Mr. Davies discloses that he is a clinical consultant for Teleflex Medical. Dr. Huang discloses a financial relationship with Windtree Therapeutics. Dr. MacIntyre discloses financial relationships with Inspirx, Ventec Life Systems, and Hillrom. All authors have completed the ICMJE uniform disclosure form.

Background: Presenting research at national and international meetings is an important aspect of the practice of respiratory care. Our department regularly presented abstracts but few projects were written up as manuscripts. We also noted that we did not have a centralized strategy to evaluate individual projects and provide mentorship. To address these challenges, we formed a Research Committee that meets monthly. We hypothesized that the formation of this committee would be associated with an increase in published manuscripts., Methods: We evaluated all original research abstracts authored or co-authored by Duke respiratory therapists presented at the AARC Open Forum between 2009 and 2019. Abstracts were grouped into two time periods; 1) 2009-2013 (before the formation of the research committee) and 2) 2014-2019 (after the formation of the research committee). Abstracts were evaluated based on authors, type of study, patient population, and whether the abstract resulted in a manuscript. Primary outcome was the percentage of abstracts published as manuscripts., Results: A total of 56 abstracts were presented by 23 different lead authors, with 16 (29%) published as manuscripts. After formation of the committee, fewer abstracts per year were presented, but these abstracts were more likely to be published as manuscripts (53% vs 18%, P = .02). For abstracts published as manuscripts, there was a significant difference in the type of study before and after committee formation ( P = .042), but there were no differences in lead author credentials, senior author credentials, author gender, or patient population., Conclusions: The formation of a research committee was associated with an increase in the percentage of abstracts published as manuscripts., Competing Interests: Mr Miller has disclosed a relationship with Ventec Life Systems and serves as Section Editor for Respiratory Care. Mr Gentile has disclosed a relationship with Teleflex Medical. Dr MacIntyre has disclosed relationships with Hillrom and Ventec Life Systems. The remaining authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4+CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain β cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, β cell survival, and response to antiinflammatory immunotherapy.

Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC ( MYC ). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor-suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation. IMPLICATIONS: These findings indicate that targeting phosphorylation of ASCL1 may offer a new approach to development of differentiation therapies in neuroblastoma. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/12/1759/F1.large.jpg., (©2020 American Association for Cancer Research.)

Penile fracture is a rare injury to the penis caused by blunt trauma. The presence of urethral injuries sustained during fracture is less than 10%, but very few cases involve complete circumferential urethral transection. We present a case of a patient who presented with traumatic penile fracture involving bilateral corporal cavernosa injury and complete urethral transection., (© 2020 The Authors.)

Objectives: To describe patterns of overall, within-household, and community adverse childhood experiences (ACEs) among children in vulnerable neighborhoods and to identify which individual ACEs, over and above overall ACE level, predict need for behavioral health services., Study Design: This was a cross-sectional study that used a sample of 257 children ages 3-16 years who were seeking primary care services with co-located mental healthcare services at 1 of 2 clinics in Chicago, Illinois. The outcome variable was need for behavioral health services (Pediatric Symptom Checklist score ≥28). The independent variables were ACEs, measured with an adapted, 28-item version of the Traumatic Events Screening Inventory., Results: Six ACE items were individually predictive of a clinical-range Pediatric Symptom Checklist score after adjusting for sociodemographic covariates: emotional abuse or neglect (OR 2.93, 95% CI 1.32-6.52, P < .01), natural disaster (OR 3.89, 95% CI 1.18-12.76, P = .02), forced separation from a parent or caregiver (OR 2.95, 95% CI 1.50-5.83, P < .01), incarceration of a family member (OR 2.43, 95% CI 1.20-4.93, P = .01), physical attack (OR 2.84, 95% CI 1.32-6.11, P < .01), and community violence (OR 2.35, 95% CI 1.18-4.65, P = .01). After adjusting for overall ACE level, only 1 item remained statistically significant: forced separation from a parent or caregiver (OR 2.44, 95% CI 1.19-5.01, P = .02)., Conclusions: ACEs that disrupt attachment relationships between children and their caregivers are a significant predictor of risk for child emotional or behavioral problems., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Noninvasive respiratory support refers to strategies aimed at providing oxygenation and/or ventilation without the use of an artificial airway. These strategies include the use of standard oxygen delivery devices (face masks, low-flow nasal cannulas), noninvasive ventilation, and high-flow nasal cannula. Considerable interest has been generated recently as to which therapy provides the optimum noninvasive support. This review examined the important literature related to noninvasive respiratory support published in 2018., (Copyright © 2019 by Daedalus Enterprises.)

Background: Tumour growth can promote the loss of muscle mass and function. This is particularly disturbing because overall survival is significantly reduced in people with weaker and smaller skeletal muscle. The risk of cancer is also greater in people who are immune deficient. Muscle wasting in mice with cancer can be inhibited by infusion of CD4 + precursor T cells that restore balanced ratios of naïve, memory, and regulatory T cells. These data are consistent with the hypothesis that stronger anti-cancer T cell immunity leads to improved muscle mass and function. As a first step to testing this hypothesis, we determined whether levels of circulating T cell subsets correlate with levels of muscle strength in people with cancer., Methods: The frequency of circulating CD4 + and CD8 + naïve, memory, and regulatory T cell subsets was quantified in 11 men with gastrointestinal cancer (aged 59.3 ± 10.1 years) and nine men without cancer (aged 60 ± 13 years), using flow cytometry. T cell marker expression was determined using real-time PCR and western blot analyses in whole blood and peripheral blood mononuclear cells. Handgrip strength, one-repetition maximum chest press, and knee extension tests were used to determine muscle strength. Performance was determined using a stair climb test. Body composition was determined using dual-energy X-ray absorptiometry scan. The Karnofsky and ECOG scales were used to assess functional impairment. Correlations between frequencies of cell subsets with strength, performance, and body composition were determined using regression analyses., Results: Our data show significant correlations between (i) higher frequencies of CD8 + naïve (P = 0.02) and effector memory (P = 0.003) T cells and lower frequencies of CD8 + central memory T cells (P = 0.002) with stronger handgrip strength, (ii) lower frequency of regulatory cells with greater lean mass index (P = 0.04), (iii) lower frequency of CD8 + T cells that express CD95 with greater stair climb power (P = 0.003), (iv) higher frequency of T cells that co-express CD197 and CD45RA and greater one-repetition maximum knee extension strength (P = 0.008), and (iv) higher expression of CD4 in whole blood with greater functional impairment (P = 0.004) in people with cancer., Conclusions: We have identified significant correlations between levels of T cell populations and muscle strength, performance, and body composition in people with cancer. These data justify a follow-up study with a larger cohort to test the validity of the findings., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Noninvasive respiratory support at the end of life is controversial, although it is becoming increasingly common. Supplemental oxygen is widely prescribed for palliative care and may help with hypoxemic respiratory failure. Noninvasive ventilation has a well-established evidence-based role in the management of respiratory failure due to exacerbations of COPD and cardiogenic pulmonary edema. However, its role during palliative care is unclear, and evidence of support is limited. High-flow nasal cannula oxygen therapy is a new strategy for which there is evidence to support its use for hypoxemic respiratory failure. However, any benefit of the use of high-flow nasal cannula oxygen therapy in the palliative setting is unknown at this time. This review examined evidence relating to the use of noninvasive respiratory support at the end of life., (Copyright © 2019 by Daedalus Enterprises.)

The superfamily of basic-Helix-Loop-Helix (bHLH) transcription factors influence cell fate in all three embryonic germ layers, and the tissue-specific class II factors have received prominent attention for their potent ability to direct differentiation during development and in cellular reprogramming. The activity of many class II bHLH proteins driving differentiation, and the inhibitory class VI bHLH factor Hes1, is controlled by phosphorylation on multiple sites by Cyclin-dependent kinases (Cdks). As class II proteins are generally thought to be active through hetero-dimerisation with the ubiquitously expressed class I E proteins, regulation of class I transcription factors such as E47 may influence the activity of multiple tissue-specific bHLH proteins. Using differentiation of nerve and muscle in Xenopus frog embryos as a model system, we set out to explore whether with the ubiquitously expressed class I E protein E47 that hetero-dimerises with Class II bHLHs to control their activity, is also regulated by multi-site phosphorylation. We demonstrate that E47 can be readily phosphorylated by Cdks on multiple sites in vitro, while ectopically-expressed E47 exists in multiple phosphorylated forms in Xenopus embryos. Preventing multi-site phosphorylation using a phospho-mutant version of E47 enhances the neurogenic and myogenic activity of three different class II bHLH reprogramming factors, and also when E47 acts in hetero-dimerisation with endogenous proteins. Mechanistically, unlike phospho-regulation of class II bHLH factors, we find that preventing phosphorylation of E47 increases the amount of chromatin-bound E47 protein but without affecting its overall protein stability. Thus, multi-site phosphorylation is a conserved regulatory mechanism across the bHLH superfamily that can be manipulated to enhance cellular differentiation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

This article asserts that U.S. demographic shifts make it imperative that academic dental institutions and, in turn, the dental profession must diversify to best meet the needs of the nation's quickly changing population. In particular, it argues that the severe underrepresentation of African American and Hispanic students in dental schools is a detriment to those students who are being excluded from a field critical to the well-being of the population, their prospective peers who are thus not afforded the benefits of compositional diversity in the classroom, and the millions of Americans who live in areas with little to no access to culturally competent oral health care. With such complex challenges facing the profession, dental schools must evolve to prepare students of all races, ethnicities, and socioeconomic backgrounds to provide adequate oral health care to the country's changing population.

Background: Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS., Methods: We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes., Results: No participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% [cohort 1]; 4.9% ± 0.28% [cohort 2]) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects., Conclusion: Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials., Trial Registration: ClinicalTrials.gov NCT02425579., Funding: NIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.

Context: In sprint events, the first 2 steps are used to accelerate the center of mass horizontally and vertically. Amputee athletes cannot actively generate energy with their running-specific prosthesis. It is likely that sprint acceleration mechanics, including step asymmetry, are altered compared with able-bodied athletes., Purpose: To investigate spatiotemporal and kinetic variables of amputee compared with able-bodied sprinters., Methods: Kinematic and kinetic data of the first and second stance were collected from 15 able-bodied and 7 amputee sprinters (2 unilateral transfemoral, 4 unilateral transtibial, and 1 bilateral transtibial) with a motion-capture system (250 Hz) and 2 force plates (1000 Hz). In addition, bilateral asymmetry was quantified and compared between groups., Results: Compared with able-bodied athletes, amputee athletes demonstrated significantly lower performance values for 5- and 10-m times. Step length, step velocity, and step frequency were decreased and contact times increased. Peak horizontal force and relative change of horizontal velocity were decreased in both stances. Peak vertical force and relative change of vertical velocity were lower for the amputee than the able-bodied group during the first stance but significantly higher during the second stance. During the first stance, able-bodied and amputee sprinters displayed a similar orientation of the ground-reaction-force vector, which became more vertically orientated in the amputee group during second stance. Amputee sprinters showed significantly greater asymmetry magnitudes for vertical force kinetics compared with able-bodietd athletes., Conclusion: A running-specific prosthesis does not replicate the function of the biological limb well in the early acceleration phase.

The proneural transcription factor Ascl1 is a master regulator of neurogenesis, coordinating proliferation and differentiation in the central nervous system. While its expression is well characterised, post-translational regulation is much less well understood. Here we demonstrate that a population of chromatin-bound Ascl1 can be found associated with short chains of ubiquitin while cytoplasmic Ascl1 harbours much longer ubiquitin chains. Only cytoplasmic ubiquitylation targets Ascl1 for destruction, which occurs by conjugation of ubiquitin to lysines in the basic helix-loop-helix domain of Ascl1 and requires the E3 ligase Huwe1. In contrast, chromatin-bound Ascl1 associated with short ubiquitin-chains, which can occur on lysines within the N-terminal region or the bHLH domain and is not mediated by Huwe1, is not targeted for ubiquitin-mediated destruction. We therefore offer further insights into post-translational regulation of Ascl1, highlighting complex regulation of ubiquitylation and degradation in the cytoplasm and on chromatin.

CD4 + T cells that co-express CD25 and CD127 (CD25 + CD127 + ) make up around 20% of all circulating CD4 + memory T cells in healthy people. The clinical significance of these cells is that in children with type 1 diabetes their relative frequency at diagnosis is significantly and directly correlated with rate of disease progression. The purpose of this study was to further characterize the CD25 + CD127 hi cells. We show that they are a mix of Th1 and Th2 cells however, they have a significantly higher relative frequency of pre-committed and committed Th2 cells, and secrete significantly higher levels of Th2-type cytokines than CD25 - memory T cells. Further, these cells are neither exhausted nor senescent and proliferate to the same extent as CD25 - memory cells. Thus, CD25 + CD127 hi cells are a highly active subset of memory T cells that might play a role in controlling inflammation via anti-inflammatory Th2-type deviation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Competing Interests: Dr MacIntyre discloses relationships with InspiRx Pharmaceuticals, Breathe Technologies, Ventec Life Support, Alana Healthcare, and Pulmonx. Mr Davies discloses a relationship with ResMed. Mr Gentile discloses relationships with Medical Dynamics and Dräger. Mr Miller has no conflicts to disclose.