Prognostic value of exercise longitudinal right ventricular free wall strain in patients with sickle cell disease.

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2 years. The cohort consisted of 87 patients (mean age was 31 ± 11 years, 66% females). All patients had normal resting TRV < 2.8 m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stress TRV and SPAP, but lower resting and peak stress TAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stress cardiac output when compared to patients with peak stress RVFWS ≥ 20% (p < 0.05). Patients with baseline peak stress RVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7 min at baseline vs. 5.5 ± 2.8 min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stress RVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up.

The Society for Pediatric Radiology Magnetic Resonance Imaging and Emergency and Trauma Imaging Committees' consensus protocol recommendation for rapid MRI for evaluating suspected appendicitis in children.

The imaging evaluation of acute abdominal pain in children with suspected appendicitis has evolved to include rapid abdominopelvic MRI (rMRI) over recent years. Through a collaborative effort between the Magnetic Resonance Imaging (MRI) and Emergency and Trauma Imaging Committees of the Society for Pediatric Radiology (SPR), we conducted a survey on the utilization of rMRI to assess practice specifics and protocols. Subsequently, we present a proposed consensus rMRI protocol derived from the survey results, literature review, and discussion and consensus between committee members.

Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.

Anaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas.

The Ethical Obligations, Barriers, and Solutions for Interprofessional Collaboration in the Treatment of Autistic Individuals.

With an estimated 1 in 44 children having been diagnosed with autism and given the variety of types of service providers that treat autism, collaboration among these professionals is a necessary part of the overall treatment package for an autistic individual. However, like with any professional skill, competence in collaborating effectively must be developed, especially because behavior analysts have been criticized for being resistant to collaboration. Competence with collaboration may be developed through coursework, professional development opportunities, and supervision by someone who has demonstrated competence with collaboration. With the 2020 update to the Ethics Code for Behavior Analysts, the behavior analyst's role in collaborating with other professionals has been clarified by several expectations. Current literature also provides additional guidance on the potential barriers to collaboration as well as recommendations for how to support a collaborative team. In order to facilitate successful collaboration, it is also important to evaluate the effectiveness of the collaborative team and to take advantage of opportunities to learn about the methodologies and perspectives of the other professionals to ensure that the client's best interests are met.

The Interplay of Permeability, Metabolism, Transporters, and Dosing in Determining the Dynamics of the Tissue/Plasma Partition Coefficient and Volume of Distribution-A Theoretical Investigation Using Permeability-Limited, Physiologically Based Pharmacokinetic Modeling.

A permeability-limited physiologically based pharmacokinetic (PBPK) model featuring four subcompartments (corresponding to the intracellular and extracellular water of the tissue, the residual plasma, and blood cells) for each tissue has been developed in MATLAB/SimBiology and applied to various what-if scenario simulations. This model allowed us to explore the complex interplay of passive permeability, metabolism in tissue or residual blood, active uptake or efflux transporters, and different dosing routes (intravenous (IV) or oral (PO)) in determining the dynamics of the tissue/plasma partition coefficient (Kp) and volume of distribution (Vd) within a realistic pseudo-steady state. Based on the modeling exercise, the permeability, metabolism, and transporters demonstrated significant effects on the dynamics of the Kp and Vd for IV bolus administration and PO fast absorption, but these effects were not as pronounced for IV infusion or PO slow absorption. Especially for low-permeability compounds, uptake transporters were found to increase both the Kp and Vd at the pseudo-steady state (Vdss), while efflux transporters had the opposite effect of decreasing the Kp and Vdss. For IV bolus administration and PO fast absorption, increasing tissue metabolism was predicted to elevate the Kp and Vdss, which contrasted with the traditional derivation from the steady-state perfusion-limited PBPK model. Moreover, metabolism in the residual blood had more impact on the Kp and Vdss compared to metabolism in tissue. Due to its ability to offer a more realistic description of tissue dynamics, the permeability-limited PBPK model is expected to gain broader acceptance in describing clinical PK and observed Kp and Vdss, even for certain small molecules like cyclosporine, which are currently treated as perfusion-limited in commercial PBPK platforms.

Kansa talk: mapping cancer terminologies in Bagamoyo, Tanzania towards dignity-based practice.

This paper reports and examines the results of qualitative research on the use of local cancer terminology in urban Bagamoyo, Tanzania. Following recent calls to unify evidence and dignity-based practices in global health, this research locates local medical sociolinguistics as a key place of entry into creating epistemologically autonomous public health practices. We used semistructured ethnographic interviews to reveal both the contextual and broader patterns related to use of local cancer terminologies among residents of Dunda Ward in urban Bagamoyo. Our findings suggest that people in Bagamoyo employ diverse terms to describe and make meanings about cancer that do not neatly fit with biomedical paradigms. This research not only opens further investigation about how ordinary people speak and make sense of the emerging cancer epidemic in places like Tanzania, but also is a window into otherwise conceptualisations of 'intervention' onto people in formerly colonised regions to improve a health situation. We argue that adapting biomedical concepts into local sociolinguistic and knowledge structures is an essential task in creating dignity-based, evidence-informed practices in global health.

Telestroke value through the eyes of emergency medicine providers: A counterfactual analysis.

Objectives: Emergency Medicine (EM) provider experiences consulting telestroke (TS) are poorly studied. In this qualitative study, we aimed to determine how TS changes patient management and to measure TS effects on EM provider confidence with acute ischemic stroke (AIS) treatment. Materials and methods: We designed a survey for EM providers querying perceptions of TS value, confidence with treating AIS, and counterfactuals regarding what EM providers would have done without TS. Eligible EM providers participated in an audio-visual TS consult within a 6-state TS network between 11/2016-11/2017. Results: We received 48 surveys (response rate 43%). The most common reason (71%) for using TS was tPA eligibility expert opinion. Most EM providers (94%) thought the patient/family were satisfied with TS and none felt their medical knowledge was doubted because of using TS. EM providers had high confidence in diagnosing AIS (95%) and tPA decision-making (86%), but not in determining thrombectomy eligibility (10%). Among EM providers who administered tPA, 85% said tPA would not have been given without TS consultation. TS consultation changed patient diagnosis in 60% of all patients and treatment plans in 56% of non-stroke patients. Most EM providers (86%) had increased confidence in their knowledge of future stroke patient management. Nearly all TS consults (93%) resulted in EM providers being more likely to use TS again. Conclusions: TS consult frequently results in both patient management change and increased EM knowledge of stroke management with increased likelihood of repeat usage. Discomfort in determining eligibility for thrombectomy points to educational opportunities.

Malpractice and Other Civil Liability in Psychedelic Psychiatry.

Psychedelics have the ability to fundamentally alter the consciousness of individuals who take them and thus pose unique legal risks for psychiatrists interested in incorporating them into their practice. Several issues related to malpractice may be relevant, including absence of standards of care, risk of harm, inappropriate treatment, and the doctrine of respondeat superior. In addition to malpractice, psychiatrists should be aware of other potential civil claims, including battery and the intentional or negligent infliction of emotional distress. Before providing psychedelic treatments to patients, psychiatrists should understand and mitigate their risk of malpractice and other civil claims.

The Importance of Sleep for Successful Neurorehabilitation after Stroke.

Sleep has important clinical implications for neurorehabilitation after stroke. We aimed to systematically explore sleep (including naps) as an essential factor in the neurorehabilitation of patients after stroke. After titles and abstracts were screened, 49 full texts were reviewed, and 7 were included in this review. Data were extracted and assessed for quality and risk of bias. We looked at any neurorehabilitation setting, and compared sleep with no sleep and explored these factors in stroke patients versus healthy individuals. Rehabilitation is critical for many activities that may need to be learned or re-learned following stroke and for returning to everyday life. In this context, sleep is essential in neurorehabilitation and physical therapy practice as it supports neuroplasticity, memory, and learning. The available data suggest that sleep should be considered in the treatment plan for successfully targeted physiotherapy to optimize cognitive and motor learning. Physical therapists should advise about sleep hygiene and therapies to improve sleep, both quality and quantity.

Bestiality Law in the United States: Evolving Legislation with Scientific Limitations.

Societies have proscribed bestiality, or sex between humans and nonhuman animals, since the earliest recorded legal codes. In the early American colonies, religious prohibitions against bestiality provided the grounds for punishing those who engaged in such acts. In the 1800's, Henry Bergh imported the animal welfare approach to the United States, which modernized the legislative treatment of animals in the country. Until recently, however, many laws in the U.S. have been outdated and vague and have utilized moralistic terminology. Since the 1960's, a growing body of literature has developed suggesting that individuals who harm animals may also interpersonally offend. This concept, known as the Link, has served as a major motivation for advocates to promote new legislation criminalizing bestiality, to modernize old state statutes, and to expand penalties for individuals convicted of having sex with animals. Unfortunately, data supporting the Link between bestiality and interpersonal violence are limited and of questionable generalizability to the broad public. The Link's weaknesses can assist in guiding further research. This article summarizes the history of bestiality law, the current state of bestiality legislation in the United States, the body of Link-related literature on bestiality and interpersonal violence and other problematic sexual behaviors, and the empirical weaknesses and needs revealed by this legislation.

Movement Disorder Specialists Survey Regarding Use of Telemedicine During the COVID-19 Pandemic.

Aim: To assess the overall satisfaction level of movement disorder specialists using a virtual platform during the COVID-19 pandemic. Methods: This was a multicenter cross-sectional survey for a 6-month period during the beginning of the COVID-19 pandemic. Movement disorder specialists, who utilized telehealth visits from March 2020 to August 2020, were included. The study surveys, including provider's satisfaction with the care that they were able to provide and visit quality, were completed by the provider after each visit. Results: A total of 206 visits, provided by movement disorder specialists, were analyzed. Zoom was the most popular platform used for remote visits (70, 34%). A backup platform was not needed in the majority of movement disorder visits (171, 83%). The majority of physicians were very satisfied or satisfied with the care provided (72.9%) and visit quality (61%). Conclusions: The satisfaction level of specialists using telemedicine during COVID-19 was high despite having encounters with elderly patients with cognitive impairment or lacking advanced skills with technology.

AUR-RRA Review: Logistics of Academic-Industry Partnerships in Artificial Intelligence.

The Radiology Research Alliance (RRA) of the Association of University Radiologists (AUR) convenes Task Forces to address current topics in radiology. In this article, the AUR-RRA Task Force on Academic-Industry Partnerships for Artificial Intelligence, considered issues of importance to academic radiology departments contemplating industry partnerships in artificial intelligence (AI) development, testing and evaluation. Our goal was to create a framework encompassing the domains of clinical, technical, regulatory, legal and financial considerations that impact the arrangement and success of such partnerships.

Sampling Thoracic Duct Lymph After Esophagectomy: A Pilot Study Investigating the "Gut-Lymph" Concept.

Background: Gut-lymph in animal models of acute disease is altered by intestinal ischemia and contributes to the development of systemic inflammation and organ dysfunction. Investigating gut-lymph in humans is hampered difficulty in accessing the thoracic duct (TD) for lymph sampling. The aims of this study were to develop and pilot a technique of intraoperative TD cannulation with delayed embolization to serially measure TD lymph pressure, flow, and composition (including markers of intestinal injury) during the early postoperative period and in response to enteral feeding and vasopressor treatment. Methods: A Seldinger technique was used for percutaneous TD cannulation during an Ivor Lewis esophagogastrectomy. Lymph flow rate and pressure were measured. TD lymph and plasma were sampled at 12 hourly intervals for up to 120 hours after surgery and before TD embolization. Biochemistry, lipids, cytokines, and markers of intestinal injury were measured before and after enteral feeding commenced at 36 hours. Results: Intraoperative TD cannulation was technically feasible in three of four patients. Delayed TD embolization was only successful in one of three patients, with two patients requiring a re-thoracotomy to treat chylothorax. Profound changes in TD composition, but not flow rate, occurred over time and in response to enteral feeding and vasopressors. TD lymph compared with plasma had significantly higher lipase (1.4-17 × ), interleukin-6 (8-108 × ), tumor necrosis factor-α (2.7-17 × ), d-lactate (0.3-23 × ), endotoxin (0.1-41 × ), and intestinal fatty acid binding protein (1.1-853 × ). Conclusions: Although TD cannulation and lymph sampling were successful, TD embolization failed in two of three patients. The composition of sampled TD lymph changed dramatically in response to enteral feeding, indicating intestinal ischemia that could be exacerbated by nonselective vasopressors. The higher concentration of proinflammatory cytokines and gut injury markers in TD lymph, compared with plasma, lends support to the gut-lymph concept.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Non-Hodgkin Lymphoma Metabolism.

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid neoplasms with different biological characteristics. About 90% of all lymphomas in the United States originate from B lymphocytes, while the remaining originate from T cells [1]. The treatment of NHLs depends on the neoplastic histology and stage of the tumor, which will indicate whether radiotherapy, chemotherapy, or a combination is the best suitable treatment [2]. The American Cancer Society describes the staging of lymphoma as follows: Stage I is lymphoma in a single node or area. Stage II is when that lymphoma has spread to another node or organ tissue. Stage III is when it has spread to lymph nodes on two sides of the diaphragm. Stage IV is when cancer has significantly spread to organs outside the lymph system. Radiation therapy is the traditional therapeutic route for localized follicular and mucosa-associated lymphomas. Chemotherapy is utilized for the treatment of large-cell lymphomas and high-grade lymphomas [2]. However, the treatment of indolent lymphomas remains problematic as the patients often have metastasis, for which no standard approach exists [2].

Children develop strong and sustained cross-reactive immune responses against spike protein following SARS-CoV-2 infection

SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population.

Serial use of existing clinical decisions aids can reduce computed tomography pulmonary angiography for pulmonary embolism.

Pulmonary embolism (PE) remains a diagnostic challenge in emergency medicine. Clinical decision aids (CDAs) like the Pulmonary Embolism Rule-Out Criteria (PERC) are sensitive but poorly specific; serial CDA use may improve specificity. The goal of this before-and-after study was to determine if serial use of existing CDAs in a novel diagnostic algorithm safely decreases the use of CT pulmonary angiograms (CTPA). This was a retrospective before-and-after study conducted at an urban ED with 105,000 annual visits. Our algorithm uses PERC, Wells' score, and D-dimer in series, before moving to CTPA. The algorithm was introduced in January, 2017. Use of CDAs and D-dimer in the 24 months pre- and 12 months post-intervention were obtained by chart review. The algorithm's effect on CTPA ordering was assessed by comparing volume 5 years pre- and 3 years post-intervention, adjusted for ED volume. Mean CTPAs per 1000 adult ED visits was 11.1 in the 5 pre-intervention years and 9.9 in the 3 post-intervention years (p < 0.0001). Use of PERC, Wells' score and D-dimer increased from 1.1%, 1.1%, and 28% to 8.8% (p = 0.0002) 8.1% (p = 0.0005), and 35% (p = 0.0066), respectively. Pre-intervention, there were six potentially missed PEs compared to three in the post-intervention period. Introduction of our serial CDA diagnostic algorithm was associated with increased use of CDAs and D-dimer and reduced CTPA rate without an apparent increase in the number of missed PEs. Prospective validation is needed to confirm these results.

Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum.

In the last few decades, there has been a resurgence in interest in the use of dietary supplements to treat diseases in humans and molybdenum has the potential to be used therapeutically. In humans, dietary molybdenum has been shown to treat iron-deficiency anemia and it may treat joint pain in arthritis. It has been proposed that the anti-anemic and tentative anti-arthritic properties of molybdenum are because it is increasing the activity of one or more mammalian molybdoenzymes. Molybdenum forms part of the active site of these enzymes. Despite this, it is unlikely that a molybdenum deficiency can develop in humans that are on an oral diet and not exposed to unsafe levels of a molybdenum antagonist. Therefore, the underlying mechanism by which dietary molybdenum treats or may treat these diseases is currently not known. This minireview examines three possible underlying mechanisms. It investigates the possibility that molybdenum: increases the quantity of active mammalian molybdoenzymes, restores or partially restores activity to malfunctioning mammalian molybdoenzymes, or blocks nuclear receptors, in cells. The examination of these mechanisms has provided an impression of the mechanism by which molybdenum treats iron-deficiency anemia and may treat arthritis; and hypothesize uses of molybdenum for other human diseases.

Performing 'the authoritative account': How the BBC's Horizon produces epistemic authority.

Viewers have often looked upon the BBC's science documentary strand, Horizon, as an authoritative source for scientific knowledge. Through interviews with the series' producers, this article examines the practices its producers perform to buttress their authority and generate the view that this show is itself a producer of knowledge, even while it is also televising and mediating science. Of particular note are references to science fiction to police boundaries between science and pseudoscience, and the use of original experimental trials to generate witnesses. These position Horizon as at least a node in the network of scientific knowledge production.