Optimizing Teamwork in the Operating Room: A Scoping Review of Actionable Teamwork Strategies.

Suboptimal teamwork in the operating room (OR) is a contributing factor in a significant proportion of preventable complications for surgical patients. Specifying behaviour is fundamental to closing evidence-practice gaps in healthcare. Current teamwork interventions, however, have yet to be synthesized in this way. This scoping review aimed to identify actionable strategies for use during surgery by mapping the existing literature according to the Action, Actor, Context, Target, Time (AACTT) framework. The databases MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC), Cochrane, Scopus, and PsycINFO were searched from inception to April 5, 2022. Screening and data extraction were conducted in duplicate by pairs of independent reviewers. The search identified 9,289 references after the removal of duplicates. Across 249 studies deemed eligible for inclusion, eight types of teamwork interventions could be mapped according to the AACTT framework: bundle/checklists, protocols, audit and feedback, clinical practice guidelines, environmental change, cognitive aid, education, and other), yet many were ambiguous regarding the actors and actions involved. The 101 included protocol interventions appeared to be among the most actionable for the OR based on the clear specification of ACCTT elements, and their effectiveness should be evaluated and compared in future work.

The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer.

Development and progression of malignancies are accompanied and influenced by alterations in the surrounding immune microenvironment. Understanding the cellular and molecular interactions between immune cells and cancer cells has not only provided important fundamental insights into the disease, but has also led to the development of new immunotherapies. The C-type lectin Dendritic Cell ImmunoReceptor (DCIR) is primarily expressed by myeloid cells and is an important regulator of immune homeostasis, as demonstrated in various autoimmune, infectious and inflammatory contexts. Yet, the impact of DCIR on cancer development remains largely unknown. Analysis of available transcriptomic data of colorectal cancer (CRC) patients revealed that high DCIR gene expression is associated with improved patients' survival, immunologically "hot" tumors and high immunologic constant of rejection, thus arguing for a protective and immunoregulatory role of DCIR in CRC. In line with these correlative data, we found that deficiency of DCIR1, the murine homologue of human DCIR, leads to the development of significantly larger tumors in an orthotopic murine model of CRC. This phenotype is accompanied by an altered phenotype of tumor-associated macrophages (TAMs) and a reduction in the percentage of activated effector CD4+ and CD8+ T cells in CRC tumors of DCIR1-deficient mice. Overall, our results show that DCIR promotes antitumor immunity in CRC, making it an attractive target for the future development of immunotherapies to fight the second deadliest cancer in the world.

UNSEG: unsupervised segmentation of cells and their nuclei in complex tissue samples.

Multiplexed imaging technologies have made it possible to interrogate complex tumor microenvironments at sub-cellular resolution within their native spatial context. However, proper quantification of this complexity requires the ability to easily and accurately segment cells into their sub-cellular compartments. Within the supervised learning paradigm, deep learning based segmentation methods demonstrating human level performance have emerged. Here we present an unsupervised segmentation (UNSEG) method that achieves deep learning level performance without requiring any training data. UNSEG leverages a Bayesian-like framework and the specificity of nucleus and cell membrane markers to construct an a posteriori probability estimate of each pixel belonging to the nucleus, cell membrane, or background. It uses this estimate to segment each cell into its nuclear and cell-membrane compartments. We show that UNSEG is more internally consistent and better at generalizing to the complexity of tissue samples than current deep learning methods. This allows UNSEG to unambiguously identify the cytoplasmic compartment of a cell, which we employ to demonstrate its use in an example biological scenario. Within the UNSEG framework, we also introduce a new perturbed watershed algorithm capable of stably and accurately segmenting a cell nuclei cluster into individual cell nuclei. Perturbed watershed can also be used as a standalone algorithm that researchers can incorporate within their supervised or unsupervised learning approaches to replace classical watershed. Finally, as part of developing UNSEG, we have generated a high-quality annotated gastrointestinal tissue dataset, which we anticipate will be useful for the broader research community. Segmentation, despite its long antecedents, remains a challenging problem, particularly in the context of tissue samples. UNSEG, an easy-to-use algorithm, provides an unsupervised approach to overcome this bottleneck, and as we discuss, can help improve deep learning based segmentation methods by providing a bridge between unsupervised and supervised learning paradigms.

Bi-functional particles for real-time phagosome acidification and proteolysis multiplex assay in macrophages.

Phagosome acidification and proteolysis are essential processes in the immune response to contain and eliminate pathogens. In recent years, there has been an increased desire for a rapid and accurate method of assessing these processes in real-time. Here, we outline the development of a multiplexed assay that allows simultaneous monitoring of phagosome acidification and proteolysis in the same sample using silica beads conjugated to pHrodo and DQ BSA. We describe in detail how to prepare the bi-functional particles and show proof of concept using differentially activated macrophages. This multiplexed spectrophotometric assay allows rapid and accurate assessment of phagosome acidification and proteolysis in real-time and could provide valuable information for understanding the immune response to pathogen invasion.

Isolation of Polystyrene Bead-Induced Phagosomes for Western Blotting.

The engulfment of "self" and "non-self" particles by immune and non-immune cells is crucial for maintaining homeostasis and combatting infection. Engulfed particles are contained within vesicles termed phagosomes that undergo dynamic fusion and fission events, which ultimately results in the formation of phagolysosomes that degrade the internalized cargo. This process is highly conserved and plays an important role in maintaining homeostasis, and disruptions in this are implicated in numerous inflammatory disorders. Given its broad role in innate immunity, it is important to understand how different stimuli or changes within the cell can shape the phagosome architecture. In this chapter, we describe a robust protocol for the isolation of polystyrene bead-induced phagosomes using sucrose density gradient centrifugation. This process results in a highly pure sample that can be used in downstream applications, namely, Western blotting.

Experimental characterization of a planar phase-engineered metamaterial lenslet for millimeter astronomy.

To unveil presently inscrutable details of the origins of our universe imprinted in the cosmic microwave background, future experiments in the millimeter and submillimeter range are focusing on the detection of fine features, which necessitate large and sensitive detector arrays to enable multichroic mapping of the sky. Currently, various approaches for coupling light to such detectors are under investigation, namely, coherently summed hierarchical arrays, platelet horns, and antenna-coupled planar lenslets. The last option offers increased bandwidth and a simpler fabrication while maintaining the desired optical performance. In this work, the design, fabrication, and experimental characterization of a prototype planar metamaterial phase-engineered lenslet operating in W-band [75 GHz; 110 GHz] is presented. Its radiated field, initially modeled and measured on a systematics-limited optical bench, is compared against a simulated hyperhemispherical lenslet, a more established technology. It is reported here that our device reaches the cosmic microwave background (CMB) specification for the next stages of experiments, demonstrating power coupling above 95% and beam Gaussicity above 97% while maintaining ellipticity below 10% and a cross-polarization level below -21d B through its operating bandwidth. Such results underline the potential advantages our lenslet can offer as focal optics for future CMB experiments.

Telemedicine among Adults Living in America during the COVID-19 Pandemic.

Background and Objectives Telemedicine can expand healthcare access to populations, but relying on technology risks a digital divide. Therefore, it is important to understand who utilizes telemedicine. This study explores telemedicine usage across socio-demographic groups in the United States during COVID-19. Methods Data came from the Household Pulse Survey (HPS) between 14 April 2021, to 11 April 2022. HPS is a rapid online response survey that assesses household experiences during COVID-19. We calculated descriptive statistics and used cross-correlation to test each pair of the time series curves. Results High school graduates used the least telemedicine (20.58%), while those with some college (23.29%) or college graduates (22.61%) had similar levels, and those with less than a high school education fluctuated over time. Black people had higher levels of use (26.31%) than Asians (22.01%). Individuals with disabilities (35.40%) used telemedicine more than individuals without disabilities (20.21%). Individuals 80 years or over (27.63%) used telemedicine more than individuals 18 to 29 years old (18.44%). Cross-correlations for the time series pairs across demographics revealed significant differences in telemedicine use for all demographic groups over time. Conclusions Overall, elderly, Black people, individuals with some college, and persons with disabilities report higher levels of telemedicine use. Telemedicine may improve healthcare access post-pandemic, but more research is needed to understand factors that drive differences among groups.

The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to bacterial infection.

Phagocytosis is a key process in innate immunity and homeostasis. After particle uptake, newly formed phagosomes mature by acquisition of endolysosomal enzymes. Macrophage activation by interferon gamma (IFN-γ) increases microbicidal activity, but delays phagosomal maturation by an unknown mechanism. Using quantitative proteomics, we show that phagosomal proteins harbour high levels of typical and atypical ubiquitin chain types. Moreover, phagosomal ubiquitylation of vesicle trafficking proteins is substantially enhanced upon IFN-γ activation of macrophages, suggesting a role in regulating phagosomal functions. We identified the E3 ubiquitin ligase RNF115, which is enriched on phagosomes of IFN-γ activated macrophages, as an important regulator of phagosomal maturation. Loss of RNF115 protein or ligase activity enhanced phagosomal maturation and increased cytokine responses to bacterial infection, suggesting that both innate immune signalling from the phagosome and phagolysosomal trafficking are controlled through ubiquitylation. RNF115 knock-out mice show less tissue damage in response to S. aureus infection, indicating a role of RNF115 in inflammatory responses in vivo. In conclusion, RNF115 and phagosomal ubiquitylation are important regulators of innate immune functions during bacterial infections.

Recordkeeping Error or Strategic Seasonal Substitution?: The Seasonality of Occupational Injuries in SOII and MarketScan.

OBJECTIVE: I compare the seasonal patterns observed in the Survey of Occupational Injuries and Illnesses (SOII) to claims data from the IBM® MarketScan® Research Databases. METHODS: I construct monthly injury rates and claims rates by supplementing occupational injuries and other claims data with hours data from the Current Population Survey and estimate seasonal effects using an Unobservable Components Model. RESULTS: While workers' compensation data and the SOII display similar seasonal patterns, the year-end decline in the MarketScan data is 1/3 to 1/2 the magnitude observed in the SOII. Short-term disability and private health insurance claims display seasonal patterns inversely related to occupational injuries. CONCLUSIONS: Part of the year-end decline in occupational injuries observed in the SOII is likely due to recordkeeping error. There is also some evidence of strategic seasonal substitution between various health-compensation alternatives.

Sixty-One-Year-Old Female With Metastatic Poorly Differentiated Carcinoma of the Appendix With Omental Metastasis.

Neuroendocrine tumors (NETs) are rare tumors that are often asymptomatic and were once considered benign. A specific subtype that we will dive into in this article is appendiceal neuroendocrine tumors (ANETS). ANETs are the most common tumors located within the appendix. Most often, they present as acute appendicitis and are found incidentally on pathology reports status post appendectomy. The objective of this article is to show that even though most of the ANETs are benign and fully treated via surgery, ANETs still have the potential to become malignant and metastasize. Our patient fits the common features seen in ANETS. She is a middle-aged woman with vague abdominal pain and no clear diagnosis on gastrointestinal (GI) workup. Computed tomography (CT) confirmed appendicitis, and pathology reports status post-surgery confirmed stage IV, pT4, Nx, M1 - poorly differentiated neuroendocrine carcinoma of the appendix with omental metastases.

Development of Flat Silicon-Based Mesh Lens Arrays for Millimeter and Sub-millimeter Wave Astronomy.

The high sensitivity requirements set by future cosmic microwave background instruments are pushing the current technologies to produce highly performant focal plane arrays with thousands of detectors. The coupling of the detectors to the telescope optics is a challenging task. Current implemented solutions include phased-array antenna-coupled detectors, platelet horn arrays, and lenslet-coupled planar antennas. There are also recent developments of flat graded-index lenses based on etched silicon. However, there are strong requirements in terms of electromagnetic performance, such as coupling efficiency and bandwidth, as well as requirements in terms of easy manufacturing and scalability, and it is very challenging to meet all these requirements with one of the above solutions. Here, we present a novel approach for producing flat metal-mesh lenslet arrays based on devices previously realized using the mesh-filter technology. We have now adapted the polypropylene-based mesh lens design to silicon substrates, thus providing a good mechanical match to the silicon-based detector arrays. The measured performance of prototype pixels operating at millimeter wavelengths is presented.

C-type Lectins in Immunity to Lung Pathogens.

The respiratory tract is tasked with responding to a constant and vast influx of foreign agents. It acts as an important first line of defense in the innate immune system and as such plays a crucial role in preventing the entry of invading pathogens. While physical barriers like the mucociliary escalator exert their effects through the clearance of these pathogens, diverse and dynamic cellular mechanisms exist for the activation of the innate immune response through the recognition of pathogen-associated molecular patterns (PAMPs). These PAMPs are recognized by pattern recognition receptors (PRRs) that are expressed on a number of myeloid cells such as dendritic cells, macrophages, and neutrophils found in the respiratory tract. C-type lectin receptors (CLRs) are PRRs that play a pivotal role in the innate immune response and its regulation to a variety of respiratory pathogens such as viruses, bacteria, and fungi. This chapter will describe the function of both activating and inhibiting myeloid CLRs in the recognition of a number of important respiratory pathogens as well as the signaling events initiated by these receptors.

Osteoarticular Infection in Three Young Thoroughbred Horses Caused by a Novel Gram Negative Cocco-Bacillus.

We describe three cases of osteoarticular infection (OAI) in young thoroughbred horses in which the causative organism was identified by MALDI-TOF as Kingella species. The pattern of OAI resembled that reported with Kingella infection in humans. Analysis by 16S rRNA PCR enabled construction of a phylogenetic tree that placed the isolates closer to Simonsiella and Alysiella species, rather than Kingella species. Average nucleotide identity (ANI) comparison between the new isolate and Kingella kingae and Alysiella crassa however revealed low probability that the new isolate belonged to either of these species. This preliminary analysis suggests the organism isolated is a previously unrecognised species.

L-DOPA causes mitochondrial dysfunction in vitro: A novel mechanism of L-DOPA toxicity uncovered.

In Parkinson's disease (PD), as in many other neurodegenerative disorders, mitochondrial dysfunction, protein misfolding, and proteotoxic stress underly the disease process. For decades, the primary symptomatic treatment for PD has been the dopamine precursor L-DOPA (Levodopa). L-DOPA however can initiate protein misfolding through its ability to mimic the protein amino acid L-tyrosine, resulting in random errors in aminoacylation and L-DOPA becoming mistakenly inserted into the polypeptide chain of proteins in place of L-tyrosine. In the present study we examined the impact that the generation of DOPA-containing proteins had on human neuroblastoma cell (SH-SY5Y) function in vitro. We showed that even in the presence of antioxidants there was a significant accumulation of cytosolic ubiquitin in DOPA-treated cells, an upregulation in the endosomal-lysosomal degradation system, deleterious changes to mitochondrial morphology and a marked decline in mitochondrial function.The effects of L-DOPA on mitochondrial function were not observed with D-DOPA, the stereoisomer of L-DOPA that cannot be inserted into proteins so did not result from oxidative stress. We could fully protect against these effects by co-treatment with L-tyrosine, supporting the view that misincorporation of L-DOPA into proteins contributed to these cytotoxic effects, leading us to suggest that co-treatment with L-tyrosine could be beneficial therapeutically.

Mycoplasma hyopneumoniae surface-associated proteases cleave bradykinin, substance P, neurokinin A and neuropeptide Y.

Mycoplasma hyopneumoniae is an economically-devastating and geographically-widespread pathogen that colonises ciliated epithelium, and destroys mucociliary function. M. hyopneumoniae devotes ~5% of its reduced genome to encode members of the P97 and P102 adhesin families that are critical for colonising epithelial cilia, but mechanisms to impair mucociliary clearance and manipulate host immune response to induce a chronic infectious state have remained elusive. Here we identified two surface exposed M. hyopneumoniae proteases, a putative Xaa-Pro aminopeptidase (MHJ_0659; PepP) and a putative oligoendopeptidase F (MHJ_0522; PepF), using immunofluorescence microscopy and two orthogonal proteomic methodologies. MHJ_0659 and MHJ_0522 were purified as polyhistidine fusion proteins and shown, using a novel MALDI-TOF MS assay, to degrade four pro-inflammatory peptides that regulate lung homeostasis; bradykinin (BK), substance P (SP), neurokinin A (NKA) and neuropeptide Y (NPY). These findings provide insight into the mechanisms used by M. hyopneumoniae to influence ciliary beat frequency, impair mucociliary clearance, and initiate a chronic infectious disease state in swine, features that are a hallmark of disease caused by this pathogen.

Vibrio cholerae residing in food vacuoles expelled by protozoa are more infectious in vivo.

Vibrio cholerae interacts with many organisms in the environment, including heterotrophic protists (protozoa). Several species of protozoa have been reported to release undigested bacteria in expelled food vacuoles (EFVs) when feeding on some pathogens. While the production of EFVs has been reported, their biological role as a vector for the transmission of pathogens remains unknown. Here we report that ciliated protozoa release EFVs containing V. cholerae. The EFVs are stable, the cells inside them are protected from multiple stresses, and large numbers of cells escape when incubated at 37 °C or in the presence of nutrients. We show that OmpU, a major outer membrane protein positively regulated by ToxR, has a role in the production of EFVs. Notably, cells released from EFVs have growth and colonization advantages over planktonic cells both in vitro and in vivo. Our results suggest that EFVs facilitate V. cholerae survival in the environment, enhancing their infectious potential and may contribute to the dissemination of epidemic V. cholerae strains. These results improve our understanding of the mechanisms of persistence and the modes of transmission of V. cholerae and may further apply to other opportunistic pathogens that have been shown to be released by protists in EFVs.

Reaction Time of Healthy Older Adults Is Reduced While Walking Fast.

Attentional requirements of walking at various speeds in older adults were examined. Twenty healthy older adults (69.9 ± 2.77 years; 8 males) were asked to walk a distance of 10 m at a self-selected speed as well as 30% quicker and 30% slower. Concurrently, reaction time (RT) was evaluated by having participants respond as fast as possible to randomly presented auditory stimuli. Results reveal that an accelerated walking speed generated faster RT than slow and self-selected speeds, while no difference was found between the latter. Faster RTs during an accelerated walking speed may have been precipitated by the reduced equilibrium demands of the task.