Applying trace element geochemistry of archaeological bone to study the coevolution of environmental change and human health in the Roman Empire.

Technological change has affected human health dating back to at least the Neolithic agricultural revolution. Growing evidence indicates widespread environmental pollution began with metallurgical practices and continues today. Environmental exposures to trace elements released from these practices have the potential to alter human body composition, such as bone mineral chemistry, especially for elements that are not homeostatically regulated. These signals can be used for inferences about human health, particularly when metallotoxins are detected in abundance. Therefore, trace element geochemistry of archaeological bone may provide a means to evaluate human health through time. However, diagenetic factors can hinder attempts to extract this information. Thus, we employed advanced analytical and interpretive methods to carefully distinct groups of European burials over about 1000 years to address questions of potentially toxic trace element exposures. Here, to address our hypothesis that Roman urbanization created one of the earliest urban toxic environment caused by multiple exposures, we present a comprehensive suite of bone trace element compositions of femora from burials spanning three distinct archaeological time periods (Bronze Age, Iron Age, and Roman period). All bone specimens were obtained from the anterior-mid shaft of carefully selected femora and processed using the same analytical techniques designed to mitigate soil contamination. Our data indicate that widespread environmental pollution accelerated in Londinium during the Roman Empire period, leading to conditions where population health would be vulnerable to environmental changes. Specifically, bone lead, silver, vanadium, arsenic, and cadmium concentrations were typically elevated and would likely be associated with multiple toxicities. In addition, bone iron levels were extremely high in some Londinium burials. Our interpretation is that the Romans inhabiting Londinium were not just poisoned by lead exposure as several previous studies show but by several metallotoxins.

Persistent headache without neurologic deficit from a spontaneous vertebral artery dissection.

INTRODUCTION: Non-traumatic headache is a common complaint seen in the emergency department (ED), accounting for 2.3% of ED visits per year in the United States (Munoz-Ceron et al., 2019). When approaching the workup and management of headache, an emergency medicine physician is tasked with generating a deadly differential by means of a thorough history and physical exam to determine the next best steps. CASE: A 21-year-old male presented to the emergency department with a debilitating new-onset headache, preceded by an isolated vertiginous event 3 days prior. He was found to have a normal neurologic examination. A non-contrast CT scan of the head revealed a large hypodensity within the left cerebellum with a subsequent MRA of the brain and neck notable for a left vertebral artery dissection, complicated by an ischemic cerebellar stroke. DISCUSSION: With an estimated incidence of 1-5 per 100,000, vertebral artery dissection is a rare cause of stroke within the general population and carries with it a high degree of morbidity and mortality (Rodallec et al., 2008). Vertebral artery dissection is a result of blood penetrating the intimal wall of the artery to form an intramural hematoma. Diagnosis can be difficult in cases presenting subacutely but a thorough history evaluating for red flags and using simple but highly sensitive exams such as the bedside HINTS exam can increase pretest probability of stroke. Clinical syndromes, red flags, and time from onset of symptoms should guide imaging modalities such as CT, CTA, MRI, and MRA in detection of small ischemic changes, intimal flaps, and luminal thromboses. CONCLUSION: Vertebral artery dissection should remain high on the differential for an emergency medicine physician when history is suggestive of a new onset headache, preceded by vertiginous symptoms. An absence of recent trauma and a normal neurologic examination does not eliminate the diagnosis.

Elevated Radium Activity in a Hydrocarbon-Contaminated Aquifer.

Hydrocarbon spills that reach the subsurface can modify aquifer geochemical conditions. Biogeochemical zones typically form proximal to the source zone that include iron (Fe(III)) and manganese (Mn(III/IV)) (hydr)oxide reduction, with potential to release associated geogenic contaminants to groundwater. Here, multi-level monitoring systems are used to investigate radium (226Ra, 228Ra) activities in an aquifer contaminated with a mixture of chlorinated solvents, ketones, and aromatics occurring as a dense non-aqueous phase liquid in the source zone. 226Ra activities are up to 10 times higher than background 60 m downgradient from the source zone, where pH is lower, total dissolved solid concentrations are higher, and conditions are methanogenic. Correlations indicate that Fe and Mn (hydr)oxide reduction and sorption site competition are likely responsible for elevated Ra activities within the dissolved phase plume. 226Ra activities return to background within the Fe(III)/SO42--reducing zone 600 m downgradient from the source, near the middle of the dissolved phase plume. Geochemical models indicate that sorption to secondary phases (e.g., clays) is important in sequestering Ra within the plume. Although maximum Ra activities within the plume are well below the U.S. drinking water standard, elevated activities compared to background emphasize the importance of investigating Ra and other trace elements at hydrocarbon-impacted sites.

Iodine speciation in deep eutectic solvents.

Iodine has been shown to act as a good electrocatalyst for metal digestion in deep eutectic solvents (DESs) but little is known about its speciation or reactivity in these high chloride containing media. Extended X-ray absorption fine structure (EXAFS) spectroscopy measurements were made at the iodine K-edge in a range of DESs with different glycolic or acidic hydrogen bond donors (HBDs), along with examining the effect of iodine concentration between 0.01 and 0.5 mol dm-3. Three groups of speciation were detected: mixed I2Cl-/I3- (glycol and lactic acid systems), mixed I3-/I2 (oxalic acid and urea systems), and singular I3- (levulinic acid system). UV-vis spectroscopy was used to confirm the speciation. Electrochemistry showed that iodine redox behaviour was unaffected by the changing speciation. Leaching data showed that metal oxidation was related not only to changing iodine speciation, but also the reactivity and coordination ability of the HBD.

Kinesiotaping for Acute Pain Due to Uncomplicated Traumatic Injury of the Shoulder or Chest Wall.

INTRODUCTION: Traumatic injuries of the shoulder or chest wall are commonly treated in the Emergency Department (ED). A complementary treatment is kinesiotaping, an elastic tape often used to treat musculoskeletal dysfunction and pain. However, the added pain-reducing effect of kinesiotape in comparison to standard conservative treatment is unknown. The aim of this study was to determine the effect of kinesiotaping on pain relief compared to standard treatment with pain medication and immobilization in patients with uncomplicated traumatic injury of the shoulder or chest wall in the ED. METHOD: A pilot randomized controlled trial (RCT) was conducted in the ED of a teaching hospital in the Netherlands from January 2021 until the end of March 2021. Patients diagnosed with uncomplicated isolated rib fractures, rib contusions, clavicle fracture, disruption of the AC joint and fracture of the proximal humerus were assigned to two treatment groups. The control group received the standard treatment with oral analgesics (acetaminophen q6h 1000 mg and NSAID (according to prescription) and if shoulder injury also a sling. The intervention group received kinesiotaping in addition to the same standard treatment. Pain intensity was measured with 0-10 Numeric Rating Scale (NRS) just before treatment (T1) and after 15 min (T2). On day 4 both groups were assessed with NRS in a follow up phone call (T3). RESULTS: A total of 251 patients presented with traumatic injury of the shoulder or chest wall in the study period, 85 patients were approached to participate and 2 of them were excluded. The remaining 83 were randomly allocated to kinesiotaping (n = 40) or control group (n = 43), 57 of them completed the study and had sufficient data for complete analysis In both groups, pain intensity after 15 min and 4 days significantly reduced compared with baseline. Regarding the reduction of pain intensity on day 4, kinesiotaping was significantly superior compared to the control group with a difference in pain reduction of 2.45 compared with 0.88 in control group (p = 0.018). CONCLUSION: Compared to standard treatment alone, kinesiotaping combined with standard care appears to be more effective in terms of acute pain reduction in patients with uncomplicated traumatic injury of the shoulder or chest wall. Further research is recommended.

Incidence of early diaphragmatic dysfunction after lung transplantation: results of a prospective observational study.

BACKGROUND: Diaphragmatic dysfunction is common after cardiothoracic surgery, but few studies report its incidence and consequences after lung transplantation. We aimed to estimate the incidence of diaphragmatic dysfunction using ultrasound in lung transplant patients up to 3 months postoperatively and evaluated the impact on clinical outcomes. METHODS: This was a single-center prospective observational cohort study of 27 lung transplant recipients using diaphragmatic ultrasound preoperatively, at 1 day, 1 week, 1 month, and 3 months postoperatively. Diaphragmatic dysfunction was defined as excursion < 10 mm in men and < 9 mm in women during quiet breathing. Clinical outcomes measured included duration of mechanical ventilation, length of stay (LOS) in Intensive Care (ICU), and hospital LOS. RESULTS: Sixty-two percentage of recipients experienced new, postoperative diaphragmatic dysfunction, but the prevalence fell to 22% at 3 months. No differences in clinical outcomes were found between those with diaphragmatic dysfunction compared to those without. Patients who experienced diaphragmatic dysfunction at 1 day postoperatively were younger and had a lower BMI than those who did not. CONCLUSIONS: Diaphragmatic dysfunction is common after lung transplant, improves significantly within 3 months, and did not impact negatively on duration of mechanical ventilation, LOS in ICU or hospital, or discharge destination.

Regional and global perspectives of honey as a record of lead in the environment.

Honey from Apis mellifera is a useful and inexpensive biomonitor for mapping metal distributions in urban centers. The sampling resolution of a biomonitoring survey (e.g., city versus global scale) determines which geochemical processes are reflected in the results. This study presents Pb isotopic compositions and metal concentrations in honey from around the world, sampled at varying resolutions: honey from Canada (n = 21), the United States (n = 111), Belgium (n = 25), and New Zealand (n = 10), with additional samples from Afghanistan, Brazil, Cuba, Germany, Liberia, Taiwan, and Turkey. Honey was sampled at high resolution in two uniquely different land-use settings (New York Metro Area and the Hawaiian island of Kaua'i), at regional-scale resolution in eastern North America (including the Great Lakes region), and Pb isotopic compositions of all samples were compared on a global scale. At high sampling resolution, metal concentrations in honey reveal spatially significant concentration gradients: in New York City, metals associated with human activity and city infrastructure (e.g., Pb, Sb, Ti, V) are more concentrated in honey collected within the city compared to honey from upstate New York, and metal concentrations in honey from Kaua'i suggest polluting effects of nearby agricultural operations. At lower resolution (regional and global scales), lead isotopic compositions of honey are more useful than metal concentrations in revealing large-scale Pb processes (e.g., the enduring legacy of global leaded gasoline use throughout the twentieth century) and the continental origin of the honey. Lead isotopic compositions of honey collected from N. America (especially from the eastern USA) are more radiogenic (206Pb/207Pb: 1.132-1.253, 208Pb/206Pb: 2.001-2.129) compared to European honey, and honey from New Zealand, which has the least radiogenic isotopic compositions measured in this study (206Pb/207Pb: 1.077-1.160, 208Pb/206Pb: 2.090-2.187). Thus, biomonitoring using honey at different resolutions reflects differing processes and, to some extent, a honey terroir defined by the Pb isotopic composition. The data presented here provide important (and current) global context for future studies that utilize Pb isotopes in honey. Moreover, this study exhibits community science in action, as most of the honey was collected by collaborators around the world, working directly with local apiarists and hobby beekeepers.

Application of Stable Isotopic Ratio Analysis to Identify the Cause of Acute Versus Chronic Lead Poisoning of a Tundra Swan (Cygnus columbianus): A Case Study.

We utilized lead (Pb) stable isotopes to identify the source of acute Pb poisoning in a Tundra Swan (Cygnus columbianus) and evaluated overall Pb exposure. Upon necropsy, we obtained samples of blood, liver, kidney, heart, thigh, breast, femur, and metallic objects (i.e., fishing sinker, spring and swivels) from the gizzard for Pb isotopic analysis. Pb isotope ratios of blood and soft tissues were essentially identical to the Pb ratios of the sinker, the likely source of acute poisoning. The spring and swivels had lower Pb content and ratios distinct from tissue, suggesting no significant contribution to poisoning. Femur Pb isotopic composition was the most distinct biological sample and indicative of a combination of sources. These results demonstrate isotopic analysis as a viable method for determining the source of acute Pb poisoning, and that Pb isotope ratios in bone most likely record a lifetime-averaged metric of Pb exposure.

Discriminant analysis and machine learning approach for evaluating and improving the performance of immunohistochemical algorithms for COO classification of DLBCL.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.

Cytotoxic Activity of a Black Bean (Phaseolus vulgaris L.) Extract and its Flavonoid Fraction in Both In Vitro and In Vivo Models of Lymphoma.

BACKGROUND: Black bean (Phaseolus vulgaris L.) is a very common legume seed in Mexican diet. Flavonoids and crude extracts from different plants have been reported as effective agents for chemoprevention and cytotoxicity in several cancer cell lines. We investigated the effects of black bean hulls extract (BBE) and its flavonoid fraction (FF) on lymphoma cells. METHODS: BBE and FF were characterized by high-performance liquid chromatography. Viability and flow cytometry assays were carried out. Finally, a mouse model was generated to test the in vivo effect of both fractions. RESULTS: Both BBE and FF inhibited cell proliferation in a dose-dependent way. In addition, cells underwent apoptosis, and the cellular population at S-phase increased after exposure to these fractions. Furthermore, mice treated with BBE or FF increased the overall survival by 5 or 6 days, respectively, in comparison with a placebo group (p = 0.056). DISCUSSION: BBE and FF had cytotoxic action by driving OCI-Ly7 cells into apoptosis as well as blocking progression to G2/M phase. In addition, BBE and FF treatments were effective in xenograft models.

Entrainment of Breast Cell Lines Results in Rhythmic Fluctuations of MicroRNAs.

Circadian rhythms are essential for temporal (~24 h) regulation of molecular processes in diverse species. Dysregulation of circadian gene expression has been implicated in the pathogenesis of various disorders, including hypertension, diabetes, depression, and cancer. Recently, microRNAs (miRNAs) have been identified as critical modulators of gene expression post-transcriptionally, and perhaps involved in circadian clock architecture or their output functions. The aim of the present study is to explore the temporal expression of miRNAs among entrained breast cell lines. For this purpose, we evaluated the temporal (28 h) expression of 2006 miRNAs in MCF-10A, MCF-7, and MDA-MB-231 cells using microarrays after serum shock entrainment. We noted hundreds of miRNAs that exhibit rhythmic fluctuations in each breast cell line, and some of them across two or three cell lines. Afterwards, we validated the rhythmic profiles exhibited by miR-141-5p, miR-1225-5p, miR-17-5p, miR-222-5p, miR-769-3p, and miR-548ay-3p in the above cell lines, as well as in ZR-7530 and HCC-1954 using RT-qPCR. Our results show that serum shock entrainment in breast cells lines induces rhythmic fluctuations of distinct sets of miRNAs, which have the potential to be related to endogenous circadian clock, but extensive investigation is required to elucidate that connection.

Effect of organic solvent additives on the enhancement of ultrasonic cavitation effects in water for lithium-ion battery electrode delamination.

Ultrasonic delamination is a low energy approach for direct recycling of spent lithium-ion batteries. The efficiency of the ultrasonic delamination relies both on the thermophysical properties (such as viscosity, surface tension, and vapour pressure) of the solvent in which the delamination process is carried out, and the properties of the ultrasound source as well as the geometry of the containment vessel. However, the effect of tailoring solutions to optimise cavitation and delamination of battery cathode coatings has not yet been sufficiently investigated. Acoustic detection, high-speed imaging, and sonochemiluminescence (SCL) are employed to study the cavitation processes in water-glycol systems and identify the effect of tailoring solvent composition on cavitation strength. The addition of small volume fractions of organic solvent (ca. 10-30 vol%), including ethylene glycol or glycerol, to the aqueous delamination solution were found to significantly improve the delamination efficiency of lithium-ion battery cathode coatings due to the alteration of these thermophysical properties. However, greater volume fractions of glycol decrease delamination efficiency due to the signal-dampening effect of viscosity on the ultrasonic waves. The findings of this study offer valuable insights for optimising ultrasonic bath solution composition to enhance film delamination processes.

A highly efficient transgene knock-in technology in clinically relevant cell types.

Inefficient knock-in of transgene cargos limits the potential of cell-based medicines. In this study, we used a CRISPR nuclease that targets a site within an exon of an essential gene and designed a cargo template so that correct knock-in would retain essential gene function while also integrating the transgene(s) of interest. Cells with non-productive insertions and deletions would undergo negative selection. This technology, called SLEEK (SeLection by Essential-gene Exon Knock-in), achieved knock-in efficiencies of more than 90% in clinically relevant cell types without impacting long-term viability or expansion. SLEEK knock-in rates in T cells are more efficient than state-of-the-art TRAC knock-in with AAV6 and surpass more than 90% efficiency even with non-viral DNA cargos. As a clinical application, natural killer cells generated from induced pluripotent stem cells containing SLEEK knock-in of CD16 and mbIL-15 show substantially improved tumor killing and persistence in vivo.

Acupuncture for treating fibromyalgia.

BACKGROUND: One in five fibromyalgia sufferers use acupuncture treatment within two years of diagnosis. OBJECTIVES: To examine the benefits and safety of acupuncture treatment for fibromyalgia. SEARCH METHODS: We searched CENTRAL, PubMed, EMBASE, CINAHL, National Research Register, HSR Project and Current Contents, as well as the Chinese databases VIP and Wangfang to January 2012 with no language restrictions. SELECTION CRITERIA: Randomised and quasi-randomised studies evaluating any type of invasive acupuncture for fibromyalgia diagnosed according to the American College of Rheumatology (ACR) criteria, and reporting any main outcome: pain, physical function, fatigue, sleep, total well-being, stiffness and adverse events. DATA COLLECTION AND ANALYSIS: Two author pairs selected trials, extracted data and assessed risk of bias. Treatment effects were reported as standardised mean differences (SMD) and 95% confidence intervals (CI) for continuous outcomes using different measurement tools (pain, physical function, fatigue, sleep, total well-being and stiffness) and risk ratio (RR) and 95% CI for dichotomous outcomes (adverse events). We pooled data using the random-effects model. MAIN RESULTS: Nine trials (395 participants) were included. All studies except one were at low risk of selection bias; five were at risk of selective reporting bias (favouring either treatment group); two were subject to attrition bias (favouring acupuncture); three were subject to performance bias (favouring acupuncture) and one to detection bias (favouring acupuncture). Three studies utilised electro-acupuncture (EA) with the remainder using manual acupuncture (MA) without electrical stimulation. All studies used 'formula acupuncture' except for one, which used trigger points.Low quality evidence from one study (13 participants) showed EA improved symptoms with no adverse events at one month following treatment. Mean pain in the non-treatment control group was 70 points on a 100 point scale; EA reduced pain by a mean of 22 points (95% confidence interval (CI) 4 to 41), or 22% absolute improvement. Control group global well-being was 66.5 points on a 100 point scale; EA improved well-being by a mean of 15 points (95% CI 5 to 26 points). Control group stiffness was 4.8 points on a 0 to 10 point; EA reduced stiffness by a mean of 0.9 points (95% CI 0.1 to 2 points; absolute reduction 9%, 95% CI 4% to 16%). Fatigue was 4.5 points (10 point scale) without treatment; EA reduced fatigue by a mean of 1 point (95% CI 0.22 to 2 points), absolute reduction 11% (2% to 20%). There was no difference in sleep quality (MD 0.4 points, 95% CI -1 to 0.21 points, 10 point scale), and physical function was not reported.Moderate quality evidence from six studies (286 participants) indicated that acupuncture (EA or MA) was no better than sham acupuncture, except for less stiffness at one month. Subgroup analysis of two studies (104 participants) indicated benefits of EA. Mean pain was 70 points on 0 to 100 point scale with sham treatment; EA reduced pain by 13% (5% to 22%); (SMD -0.63, 95% CI -1.02 to -0.23). Global well-being was 5.2 points on a 10 point scale with sham treatment; EA improved well-being: SMD 0.65, 95% CI 0.26 to 1.05; absolute improvement 11% (4% to 17%). EA improved sleep, from 3 points on a 0 to 10 point scale in the sham group: SMD 0.40 (95% CI 0.01 to 0.79); absolute improvement 8% (0.2% to 16%). Low-quality evidence from one study suggested that MA group resulted in poorer physical function: mean function in the sham group was 28 points (100 point scale); treatment worsened function by a mean of 6 points (95% CI -10.9 to -0.7). Low-quality evidence from three trials (289 participants) suggested no difference in adverse events between real (9%) and sham acupuncture (35%); RR 0.44 (95% CI 0.12 to 1.63).Moderate quality evidence from one study (58 participants) found that compared with standard therapy alone (antidepressants and exercise), adjunct acupuncture therapy reduced pain at one month after treatment: mean pain was 8 points on a 0 to 10 point scale in the standard therapy group; treatment reduced pain by 3 points (95% CI -3.9 to -2.1), an absolute reduction of 30% (21% to 39%). Two people treated with acupuncture reported adverse events; there were none in the control group (RR 3.57; 95% CI 0.18 to 71.21). Global well-being, sleep, fatigue and stiffness were not reported. Physical function data were not usable.Low quality evidence from one study (38 participants) showed a short-term benefit of acupuncture over antidepressants in pain relief: mean pain was 29 points (0 to 100 point scale) in the antidepressant group; acupuncture reduced pain by 17 points (95% CI -24.1 to -10.5). Other outcomes or adverse events were not reported.Moderate-quality evidence from one study (41 participants) indicated that deep needling with or without deqi did not differ in pain, fatigue, function or adverse events. Other outcomes were not reported.Four studies reported no differences between acupuncture and control or other treatments described at six to seven months follow-up.No serious adverse events were reported, but there were insufficient adverse events to be certain of the risks. AUTHORS' CONCLUSIONS: There is low to moderate-level evidence that compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with fibromyalgia. There is moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture in reducing pain or fatigue, or improving sleep or global well-being. EA is probably better than MA for pain and stiffness reduction and improvement of global well-being, sleep and fatigue. The effect lasts up to one month, but is not maintained at six months follow-up. MA probably does not improve pain or physical functioning. Acupuncture appears safe. People with fibromyalgia may consider using EA alone or with exercise and medication. The small sample size, scarcity of studies for each comparison, lack of an ideal sham acupuncture weaken the level of evidence and its clinical implications. Larger studies are warranted.

The influence of mental toughness and self-regulation on post-season perceptions in varsity athletes.

OBJECTIVE: To investigate whether pre-season self-reported mental toughness and self-regulation strategies predicts post-season stress, mental health, group cohesion, and satisfaction in varsity athletes. PARTICIPANTS: Sixty-seven varsity athletes from a U-Sport Canadian university. METHODS: Athletes completed pre- and post-season measures of mental toughness, emotion regulation, self-control, group cohesion, and satisfaction. Multiple mediation models were employed during analyses. RESULTS: Pre-season emotion regulation was a significant mediator for the relationships between mental toughness and post-season ratings of perceived stress, perceived mental health, and group cohesion. Self-control was not a significant mediator. CONCLUSIONS: Emotion regulation plays a significant role in an athlete's experience of perceived stress, mental health issues, and their ratings of group cohesiveness. Research on student-athlete health may benefit from examining emotion regulation training techniques.

The effect of a structured ECPR protocol aided by specific simulation training in a quaternary ECMO centre: A retrospective pre-post study.

Background: There is limited literature exploring the relationship between simulation training and extracorporeal cardiopulmonary resuscitation (ECPR) outcomes. We examined whether there was an association between the implementation of an in situ simulation training program and ECPR utilisation, time to extracorporeal membrane oxygenation (ECMO), and neurologically intact survival. Methods: In this retrospective pre-post study of in-hospital cardiac arrests (IHCA) and out-of-hospital cardiac arrests (OHCA), we analysed data for all patients recorded as receiving ECPR from September 2009 to December 2020 at our institution, relative to the implementation of an in situ ECPR simulation training program and a standardised procedure for high-quality ECPR. The primary outcome was Cerebral Performance Category (CPC) 1 or 2 at hospital discharge. Results: There were 27 patients in the pre-intervention period and 39 patients in the post-intervention period. The median ECPR rate per year was 2 pre-intervention and 7 post-intervention (p = 0.073). There was an association between the implementation of the program and decreased median time from OHCA to ECMO flow, from 87 (IQR 78-95) minutes pre-intervention to 70 (IQR 69-72) minutes post-intervention (p = 0.002). Median time from IHCA to ECMO flow was 40 (IQR 20-75) minutes pre-intervention and 28 (IQR 16-41) minutes post-intervention (p = 0.134). Survival with CPC 1 or 2 was 7/27 (25.9%) pre-intervention and 15/39 (38.5%) post-intervention (p = 0.288). Conclusion: We observed an association between the implementation of an ECPR-specific simulation program and decreased time from OHCA to ECMO flow. There was no association between the implementation of the program and neurologically intact survival at hospital discharge.

Lung ultrasound score as an indicator of dynamic lung compliance during veno-venous extra-corporeal membrane oxygenation.

Decisions on weaning from veno-venous extra-corporeal membrane oxygenation (VV-ECMO) requires the ability to maintain adequate gas exchange and work of breathing with reductions in ECMO pump flow and fresh gas flow. Testing of the readiness to wean the patient from ECMO however may vary dependent upon local protocols and clinical judgment. This study sought to validate the use of the LUS-score during VV-ECMO against the changes in chest x-ray infiltrates, dynamic lung compliance (CLdyn) and VV-ECMO settings (as standard measures of native lung function and the level of ECMO support) during the ECMO cycle. This prospective cohort study of 10 patients on VV-ECMO compared the LUS score (range 0-36) within 48-h, day 5 and day 10 of commencement of ECMO (or on the day of ECMO decannulation) to dynamic lung compliance, Murray Lung Injury Score and ECMO settings. Seven Male and three Female patients were included (average age 37 years (SD 14.8) and weight 71 Kg (SD 16.9). Median (IQR) duration of ECMO, ICU and hospital length of stay was 7.5 days (5.2-19.0), 12.5 days (8.5-22.7), 19.0 days (12.1- 36.1), respectively. There was a strong negative association between LUS-score and dynamic lung compliance (rs(33) = -0.66, p < .001) providing some validation on the use of the LUS score as a potential surrogate measure of lung aeration and lung mechanics during VV-ECMO weaning.

Penile Dorsal Vein Rupture Identified by Emergency Department Ultrasound.

CASE PRESENTATION: We present the case of a young male with high clinical suspicion of a penile fracture found to have dorsal vein rupture by emergency department point-of-care ultrasound. This false form of penile fracture was subsequently confirmed intraoperatively. DISCUSSION: Penile fracture is a rare clinical entity that may be separated into true vs false penile fracture, with only true fracture requiring surgery. The images submitted here add to the sparse literature evidence that point-of-care ultrasound can be used to differentiate between these two clinical entities. Additionally, this case report highlights an opportunity for further research into and application of point-of-care ultrasound to the evaluation of suspected penile fractures.

AsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines.

Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we isolate an engineered variant, "AsCas12a Ultra", that increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We show that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.

Dyselectrolytemias and arrhythmias.

Critical care patients are submitted to multiple derangements of vital parameters. Even in patients with a normally performing heart, its electrical activity can be strongly influenced by dyselectrolytemias, acid-base imbalance and aggressive drug therapy. In this paper, the basic principles of the electrophysiologic properties of the heart are reviewed, and the impact of dyselectrolytemias on heart excitability are underlined. Some clinically relevant aspects are described in greater depth, with respect to life-threatening arrhythmias.