A New Type of Programmed Cell Death in C. Elegans

The most intensively studied form of programmed cell death (PCD) is apoptosis, which is characterized by stereotypical morphological features including chromatin compaction and by a requirement for the activity of caspase proteases, which are controlled by conserved gene pathways. Although non-apoptotic, caspase-independent programmed cell death pathways have been postulated, there is little evidence to convincingly prove their existence, and few insights regarding their molecular basis or possible in vivo functions. To investigate this question, we have studied the developmentally regulated PCD of the Caenorhabditis elegans linker cell. We have carried out transmission electron microscopy studies of dying linker cells, which revealed non-apoptotic features, including nuclear crenellation in the absence of chromatin condensation, swelling of mitochondria and endoplasmic reticulum, and accumulation of cytoplasmic single- and multilayered membrane-bound structures. Similar morphological changes occur during the normal developmental death of some vertebrate neurons in the spinal cord and ciliary ganglia, suggesting that this is a highly conserved cell death program. Our genetic studies demonstrate that linker cell death is a non-apoptotic programmed cell death. This cell death is independent of the ced-3 caspase, other C. elegans caspase homologs, and can occur even when a broad-spectrum caspase inhibitor is expressed. We have found that the engulfment of the linker cell is independent of the known C. elegans engulfment genes. We tested and found no evidence for the involvement of autophagic, necrotic, or Wallerian degeneration genes in linker cell death. By ablating cells neighboring the linker cell, and by examining mutants in which the linker cell is abnormally positioned, we demonstrated that the linker cell employs a cell-autonomous program to promote its demise. Using a candidate gene approach, we showed that linker cell death is controlled by the microRNA let-7 and by the zinc finger transcription factor lin-29, both components of the main developmental timing pathway in the animal. Conducting a genome-wide RNAi screen, we have identified new candidate regulators of linker cell death. Characterization of these genes may uncover the molecular mechanism driving this new type of programmed cell death in C. elegans

The Rhetoric of the Troubadours

The medieval troubadours were no wandering musicians, casually improvising their songs as they strolled from town to town, but trained artists who lovingly crafted their songs to please and woo their listeners. The art of rhetoric deeply affected the art of the troubadour. First, the art of rhetoric divided composition of a speech into five well-defined parts. The troubadours consciously molded their songs according to these parts. Second, the medieval troubadour theorists then developed a system of genres, adding their own layer to the ancient art of rhetoric. Each genre demanded a specific topic, such as love, and a peculiar approach to that topic. Finally, the art of rhetoric also inspired a close union of the poems and their melodies. The troubadours were no wandering musicians, casually improvising their songs as they strolled from town to town, but trained artists who lovingly crafted their songs to please and woo their listeners

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Presyncope Is Associated with Intensive Care Unit Admission in Emergency Department Patients with Acute Pulmonary Embolism

Introduction: Syncope is common among emergency department (ED) patients with acute pulmonary embolism (PE) and indicates a higher acuity and worse prognosis than in patients without syncope. Whether presyncope carries the same prognostic implications has not been established. We compared incidence of intensive care unit (ICU) admission in three groups of ED PE patients: those with presyncope; syncope; and neither.Methods: This retrospective cohort study included all adults with acute, objectively confirmed PE in 21 community EDs from January 2013–April 2015. We combined electronic health record extraction with manual chart abstraction. We used chi-square test for univariate comparisons and performed multivariate analysis to evaluate associations between presyncope or syncope and ICU admission from the ED, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI).Results: Among 2996 PE patients, 82 (2.7%) had presyncope and 109 (3.6%) had syncope. ICU admission was similar between groups (presyncope 18.3% vs syncope 25.7%) and different than their non-syncope counterparts (either 22.5% vs neither 4.7%; p<0.0001). On multivariate analysis, both presyncope and syncope were independently associated with ICU admission, controlling for demographics, higher-risk PE Severity Index (PESI) class, ventilatory support, proximal clot location, and submassive and massive PE classification: presyncope, aOR 2.79 (95% CI, 1.40, 5.56); syncope, aOR 4.44 (95% CI 2.52, 7.80). These associations were only minimally affected when excluding massive PE from the model. There was no significant interaction between either syncope or presyncope and PESI, submassive or massive classification in predicting ICU admission.Conclusion: Presyncope appears to carry similar strength of association with ICU admission as syncope in ED patients with acute PE. If this is confirmed, clinicians evaluating patients with acute PE may benefit from including presyncope in their calculus of risk assessment and site-of-care decision-making

Quantity of Vaccine Poliovirus Shed Determines the Titer of the Serum Neutralizing Antibody Response in Indian Children Who Received Oral Vaccine

Replication of oral poliovirus vaccine (OPV) in the intestine (ie, vaccine take) is associated with seroconversion and protection against poliomyelitis. We used quantitative polymerase chain reaction analysis to measure vaccine shedding in 300 seronegative infants aged 6–11 months and in 218 children aged 1–4 years 7 days after administration of monovalent or bivalent OPV. We found that the quantity of shedding correlated with the magnitude of the serum neutralizing antibody response measured 21 or 28 days after vaccination. This suggests that the immune response to OPV is on a continuum, rather than an all-or-nothing phenomenon, that depends on efficient vaccine virus replication

A multi- and mixed-method adaptation study of a patient-centered perioperative mental health intervention bundle

BACKGROUND: Anxiety and depression are common among older adults and can intensify during perioperative periods, but few mental health interventions are designed for older surgical patients\u27 unique needs. As part of the feasibility trial, we developed and adapted a perioperative mental health (PMH) bundle for older patients comprised of behavioral activation (BA) and medication optimization (MO) to ameliorate anxiety and depressive symptoms before, during, and after cardiac, orthopedic, and oncologic surgery. METHODS: We used mixed-methods including workshop studios with patients, caregivers, clinicians, researchers, and interventionists; intervention refinement and reflection meetings; patient case review meetings; intervention session audio-recordings and documentation forms; and patient and caregiver semi-structured interviews. We used the results to refine our PMH bundle. We used multiple analytical approaches to report the nature of adaptations, including hybrid thematic analysis and content analysis informed by the Framework for Reporting Adaptations and Modifications - Expanded. RESULTS: Adaptations were categorized by content (intervention components), context (how the intervention is delivered, based on the study, target population, intervention format, intervention delivery mode, study setting, study personnel), training, and evaluation. Of 51 adaptations, 43.1% involved content, 41.2% involved context, and 15.7% involved training and evaluation. Several key adaptations were noted: (1) Intervention content was tailored to patient preferences and needs (e.g., rewording elements to prevent stigmatization of mental health needs; adjusting BA techniques and documentation forms to improve patient buy-in and motivation). (2) Cohort-specific adaptations were recommended based on differing patient needs. (3) Compassion was identified by patients as the most important element. CONCLUSIONS: We identified evidence-based mental health intervention components from other settings and adapted them to the perioperative setting for older adults. Informed by mixed-methods, we created an innovative and pragmatic patient-centered intervention bundle that is acceptable, feasible, and responsive to the needs of older surgical populations. This approach allowed us to identify implementation strategies to improve the reach, scalability, and sustainability of our bundle, and can guide future patient-centered intervention adaptations. CLINICAL TRIALS REGISTRATION: NCT05110690 (11/08/2021)

py4DSTEM: a software package for multimodal analysis of four-dimensional scanning transmission electron microscopy datasets

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full 2D image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields and other sample-dependent properties. However, extracting this information requires complex analysis pipelines, from data wrangling to calibration to analysis to visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail, and present results from several experimental datasets. We have also implemented a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open source HDF5 standard. We hope this tool will benefit the research community, helps to move the developing standards for data and computational methods in electron microscopy, and invite the community to contribute to this ongoing, fully open-source project