Search

Sofia V Krylova, Sara Glickman, Ali Kalam, Katherine Chemakin, Joseph Yi, Linda Forrester, Priti Mishall, Adi Pinkas Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USACorrespondence: Adi Pinkas, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, F620S, Bronx, NY, 10461, USA, Email adi.pinkas@einsteinmed.eduAbstract: The thoracic cavity contains vital cardiovascular and pulmonary structures. Few congenital anatomical variations in the bronchial tree and pulmonary vasculature have been reported. Understanding such variants is crucial during surgical procedures that involve the thorax. During routine dissection of an 89-year-old male cadaver as part of a first-year anatomy course, an anomaly of the bronchial tree was discovered. The left lung hilum was notable for the pulmonary artery being posterior to the mainstem bronchus. The case report describes normal lung development and anatomy and the significance of this novel variation in which has not been previously described in the literature.Keywords: pulmonary artery, bronchus, lung, pulmonary vein, thoracic region

Abstract Background Limited research has explored the effect of Circle of Willis (CoW) anatomy among blunt cerebrovascular injuries (BCVI) on outcomes. It remains unclear if current BCVI screening and scanning practices are sufficient in identification of concomitant COW anomalies and how they affect outcomes. Methods This retrospective cohort study included adult traumatic BCVIs at 17 level I-IV trauma centers (08/01/2017-07/31/2021). The objectives were to compare screening criteria, scanning practices, and outcomes among those with and without COW anomalies. Results Of 561 BCVIs, 65% were male and the median age was 48 y/o. 17% (n = 93) had a CoW anomaly. Compared to those with normal CoW anatomy, those with CoW anomalies had significantly higher rates of any strokes (10% vs. 4%, p = 0.04), ICHs (38% vs. 21%, p = 0.001), and clinically significant bleed (CSB) before antithrombotic initiation (14% vs. 3%, p

The grass subspecie (ssp.) Vulpia ambigua is devoid of long hairs on its stiffly erect and very narrow inflorescence. It exhibits a purplish coloring at fruiting. It is generally smaller in all its parts as compared to the subspecie Vulpa ciliata. A distinctive feature of the ssp. ambigua is the very unequal length of its two glumes. V. ciliata belongs to the Mediterranean-Atlantic portion of the United Kingdom while ssp. ambigua is limited to England, Wales and the Channel Islands.

Ahmad F Bayomy,1 Lynn Ann Forrester,1 Stephen G Crowley,2 Charles A Popkin1 1Department of Orthopedic Surgery, Columbia University Medical Center, New York, NY, USA; 2Department of Orthopedic Surgery, Albany Medical College, Albany, NY, USACorrespondence: Charles A PopkinDepartment of Orthopedic Surgery, Columbia University Medical Center, 3959 Broadway 8 th Floor, New York, NY 10032, USATel +1 (212) 305-4787Email cp2654@cumc.columbia.eduAbstract: The use of eponyms in the orthopedics literature has come under scrutiny, and there is a growing body of literature evaluating the utility of these terms in modern healthcare delivery. Although the field of pediatric orthopedic sports medicine is a relatively modern subspecialty, it is built on a foundation of over 100 years of pediatric musculoskeletal medicine. As a result, eponyms account for a significant portion of the vernacular used in the field. The purpose of this review is to summarize and describe the history of common eponyms relevant to pediatric sports pathology, examination maneuvers, classification systems, and surgical procedures. Use of eponyms in medicine is flawed. However, an improved understanding of these terms allows for informed use in future scientific discourse, patient care and medical education and may encourage future innovation and research into understanding pediatric orthopedic pathologies.Keywords: eponyms, orthopedics, sports medicine, pediatrics, Galeazzi, Greulich, Pyle, Beighton, Horan, apophysitis

What is known and objective Clostridium difficile infection ( CDI) represents a spectrum of disease and is a significant concern for healthcare institutions. Our study objective was to assess whether implementation of a regional CDI management policy with Clinical Pharmacy and Medical Microbiology and Infection Control involvement would lead to an improvement in concordance in prescribing practices to an evidence-based CDI disease severity assessment and pharmacological treatment algorithm. Methods Conducted at a tertiary care teaching hospital, this two-phase quality assurance study consisted of a baseline retrospective healthcare record review of patients with CDI prior to the implementation of a regional CDI management policy followed by a prospective evaluation post-implementation. Results and discussion One hundred and forty-one CDI episodes in the pre-implementation group were compared to 283 episodes post-implementation. Overall treatment concordance to the CDI treatment algorithm was achieved in 48 of 141 cases (34%) pre-implementation compared with 136 of 283 cases (48·1%) post-implementation ( P = 0·01). The median time to treatment with vancomycin was reduced from five days to one day ( P < 0·01), with median length of hospital stay decreasing from 30 days to 21 days ( P = 0·01) post-implementation. There was no difference in 30-day all-cause mortality. What is new and conclusion A comprehensive approach with appropriate stakeholder involvement in the development of clinical pathways, education to healthcare workers and prospective audit with intervention and feedback can ensure patients diagnosed with CDI are optimally managed and prescribed the most appropriate therapy based on CDI disease severity. [ABSTRACT FROM AUTHOR]

Summary Background Pre-operative decolonization therapy (DcTx) using chlorhexidine (CHG) body washes and/or intranasal mupirocin can reduce surgical site infections (SSIs), but compliance is often suboptimal. Aim To assess the effectiveness of immediate DcTx using a novel approach of intranasal antimicrobial photodisinfection therapy (PDT) combined with CHG body wipes for the reduction of SSIs. Methods Between 1 st September 2011 and 31 st August 2012, 3068 elective cardiac, orthopaedic, spinal, vascular, thoracic and neurosurgical patients were treated with CHG in the 24 h preceding surgery, and received intranasal PDT in the pre-operative area. SSI surveillance methodology remained unchanged from previous years and patients were followed for one year. Results were compared with those for a four-year historical control group of 12,387 patients as well as those for a concurrent control group of 206 untreated patients. Findings A significant reduction in the SSI rate was observed between treated patients and the historical control group [1.6% vs 2.7%, P = 0.0004, odds ratio (OR) 1.73, 95% confidence interval (CI) 1.2815–2.3453]. This significant reduction was maintained on intent-to-treat analysis ( P = 0.021, OR 1.37, 95% CI 1.9476–1.7854). Overall compliance with DcTx was 94%. A 1:4 propensity score analysis of matched treated and untreated patients demonstrated that DcTx reduced the risk of SSIs significantly ( P = 0.00026, z = 3.65). Conclusion The combination of CHG wipes and PDT immediately before surgery reduced SSIs, achieved excellent compliance, and was easily integrated into the pre-operative routine. [ABSTRACT FROM AUTHOR]

Summary: Data on healthcare workers''(HCWs) self-reported knowledge regarding selection of facial protection equipment, usage preferences and compliance are limited. We used a questionnaire on the use of facial protection equipment at a 700-bed adult tertiary care hospital employing approximately 7000 HCWs. Clinical areas targeted were those with frequent users of N95 respirators: intensive care unit, emergency room, respiratory services, and internal medicine. Respiratory therapists were also invited. In all, 137 questionnaires (68.5%) were returned. Most (72.8%) reported that training on the use of facial protection equipment was ‘sufficient’ to ‘excellent’. The PFR95 and 3M 1860 Cone were used most frequently (56%) followed by the 3M 1870 Pocket (42%). While 95% reported having been fit-tested, only 60% were tested annually. PRF95 use exceeded the number of HCWs fit-tested for the item. Overall comfort and compliance scores were 13.6/20 and 21.5/25, respectively, for respirators and 7.7/10 and 18.5/25 for protective eyewear. No relationship between comfort and years of use of either respirators or protective eyewear was found. The results highlight potential failures in effectiveness in the use of personal protective equipment that could compromise HCW safety, and support observations that compliance in the workplace is usually less than in the research setting. [Copyright &y& Elsevier]

The purpose of this study was to determine whether peripheral arterial disease (PAD) subjects had impaired temporal and spatial gait characteristics compared to non-PAD controls at preferred and rapid self-selected walking paces. A total of 28 PAD subjects with intermittent claudication (age = 71 ± 1; mean ± SEM) and 15 non-PAD controls with at least one cardiovascular risk factor but no ambulatory leg pain (age = 71 ± 1) were recruited. Gait parameters consisting of velocity, cadence, stride length, swing time, stance time, single-support time, double-support time, and base of support were recorded at the preferred and rapid walking paces. At the rapid walking pace, velocity was 22% slower ( p, 0.001) in the PAD subjects compared with the non-PAD controls (99.9 ± 3.3 vs. 117.5 ± 5.3 cm/s) due to an 8% ( p= 0.019) slower cadence (99.9 ± 1.7 vs. 103.3 ± 2.4 steps/min) and a 14% ( p, 0.001) shorter stride length (119.8 ± 2.9 vs. 135.8 ± 4.2 cm/stride). The PAD subjects spent 5% less of the gait cycle in the swing phase ( p= 0.006) and 3% more in stance ( p= 0.006) than their non-PAD counterparts. During the stance phase, the PAD subjects spent 5% less of the gait cycle in single-stance ( p= 0.004) and 16% more in double-stance ( p= 0.007). Similar results were obtained at the preferred walking pace. In conclusion, compared with the controls, PAD subjects adopted an ambulatory pattern that favored greater gait stability at the expense of greater walking speed at either their preferred or rapid self-selected paces. [ABSTRACT FROM AUTHOR]

Interrogative suggestibility refers to the tendency of individuals to accept suggestive information in an interrogative context. Within the criminal justice system, this factor has substantial implications in relation to the obtaining of written statements, admissions from suspects, and, most importantly, false confessions. Gudjonsson and Clark (1986) have developed a theoretical model of suggestibility, and contend that suggestibility is mediated by an individual's cognitive abilities, mental state and personality characteristics. In particular, they emphasise the role of coping strategies, positing that active/problem‐focused coping strategies lead to greater resistance to suggestive information whilst avoidant/emotion‐focused strategies lead to increased susceptibility to accepting suggestive information. The current study evaluated this aspect of Gudjonsson and Clark's (1986) model, using the Gudjonsson Suggestibility Scale (Gudjonsson, 1984) and the COPE (Carver, Scheier & Weintraub, 1989) inventory. Additionally, it was evaluated whether dispositional or situational coping strategies would be a better predictor of interrogative suggestibility. Sixty‐one participants completed both measures in the belief that they were participating in an investigation into memory. The results failed to support the hypothesized relationship between methods of coping and levels of interrogative suggestibility. Additionally, neither situational nor dispositional coping strategies were found to better predict interrogative suggestibility. The results are discussed in terms of Gudjonsson's (1988) previous findings and current theories on coping behaviour. [ABSTRACT FROM PUBLISHER]

The nucleotide sequence of the Escherichia coli enterobactin biosynthesis gene entD has been determined. entD specifies a predicted 23579 Dalton protein containing several helical regions, a transmembrane segment and one positively charged domain. The EntD polypeptide was overexpressed and identified in electrophoretic gels as a membrane protein. Although results of conventional membrane fractionation techniques were inconclusive, protease accessibility studies provided evidence that EntD domains are exposed on the inner leaflet of the cytoplasmic membrane. The presence of repetitive extragenic palindromic (REP) sequences within the fepA-entD intercistronic region was confirmed. Lack of a canonical promoter and an iron control region 5′ to entD, along with RNA hybridization data, suggest that an iron-regulated transcript contains both fepA and entD. [ABSTRACT FROM AUTHOR]

One target for rehabilitating locomotor disorders in older adults is to increase mobility by improving walking velocity. Combining rhythmic auditory cueing (RAC) and treadmill training permits the study of the stride length/stride velocity ratio (SL/SV), often reduced in those with mobility deficits. We investigated the use of RAC to increase velocity by manipulating the SL/SV ratio in older adults. Nine participants (6 female; age: 61.1 ± 8.8 years) walked overground on a gait mat at preferred and fast speeds. After acclimatization to comfortable speed on a treadmill, participants adjusted their cadence to match the cue for 3 min at 115% of preferred speed by either (a) increasing stride length only or (b) increasing stride frequency only. Following training, participants walked across the gait mat at preferred velocity without, and then with, RAC. Group analysis determined no immediate overground velocity increase, but reintroducing RAC did produce an increase in velocity after both conditions. Group and single subject analysis determined that the SL/SV ratio changed in the intended direction only in the stride length condition. We conclude that RAC is a powerful organizer of gait parameters, evidenced by its induced after-effects following short duration training. [ABSTRACT FROM AUTHOR]

The ability to differentiate genetically modified mouse embryonic stem (ES) cells into functional macrophages provides a potentially attractive resource to study host-pathogen interactions without the need for animal experimentation. This is particularly useful in instances where the gene of interest is essential and a knockout mouse is not available. Here we differentiated mouse ES cells into macrophages in vitro and showed, through a combination of flow cytometry, microscopic imaging, and RNA-Seq, that ES cell-derived macrophages responded to S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages. We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is known to play a role in tumour necrosis factor-α signalling but has not been studied for its role in infections or response to Toll-like receptor agonists. Interestingly, traf2-deficient macrophages produced reduced levels of inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin stimulation and exhibited increased susceptibility to S. Typhimurium infection. [ABSTRACT FROM AUTHOR]

Abstract Background Hemiparesis after stroke often leads to impaired ankle motor control that impacts gait function. In recent studies, robotic devices have been developed to address this impairment. While capable of imparting forces to assist during training and gait, these devices add mass to the paretic leg which might encumber patients' gait pattern. The purpose of this study was to assess the effects of the added mass of one of these robots, the MIT's Anklebot, while unpowered, on gait of chronic stroke survivors during overground and treadmill walking. Methods Nine chronic stroke survivors walked overground and on a treadmill with and without the anklebot mounted on the paretic leg. Gait parameters, interlimb symmetry, and joint kinematics were collected for the four conditions. Repeated-measures analysis of variance (ANOVA) tests were conducted to examine for possible differences across four conditions for the paretic and nonparetic leg. Results The added inertia and friction of the unpowered anklebot had no statistically significant effect on spatio-temporal parameters of gait, including paretic and nonparetic step time and stance percentage, in both overground and treadmill conditions. Noteworthy, interlimb symmetry as characterized by relative stance duration was greater on the treadmill than overground regardless of loading conditions. The presence of the unpowered robot loading reduced the nonparetic knee peak flexion on the treadmill and paretic peak dorsiflexion overground (p < 0.05). Conclusions Our results suggest that for these subjects the added inertia and friction of this backdriveable robot did not significantly alter their gait pattern.

Abstract Background The rodent specific reproductive homeobox (Rhox) gene cluster on the X chromosome has been reported to contain twelve homeobox-containing genes, Rhox1-12. Results We have identified a 40 kb genomic region within the Rhox cluster that is duplicated eight times in tandem resulting in the presence of eight paralogues of Rhox2 and Rhox3 and seven paralogues of Rhox4. Transcripts have been identified for the majority of these paralogues and all but three are predicted to produce full-length proteins with functional potential. We predict that there are a total of thirty-two Rhox genes at this genomic location, making it the most gene-rich homoeobox cluster identified in any species. From the 95% sequence similarity between the eight duplicated genomic regions and the synonymous substitution rate of the Rhox2, 3 and 4 paralogues we predict that the duplications occurred after divergence of mouse and rat and represent the youngest homoeobox cluster identified to date. Molecular evolutionary analysis reveals that this cluster is an actively evolving region with Rhox2 and 4 paralogues under diversifying selection and Rhox3 evolving neutrally. The biological importance of this duplication is emphasised by the identification of an important role for Rhox2 and Rhox4 in regulating the initial stages of embryonic stem (ES) cell differentiation. Conclusion The gene rich Rhox cluster provides the mouse with significant biological novelty that we predict could provide a substrate for speciation. Moreover, this unique cluster may explain species differences in ES cell derivation and maintenance between mouse, rat and human.

Breast cancer screening performance of supplemental imaging modalities by breast density and breast cancer risk has not been widely studied, and the optimal choice of modality for women with dense breasts remains unclear in clinical practice and guidelines. This systematic review aimed to assess breast cancer screening performance of supplemental imaging modalities for women with dense breasts, by breast cancer risk. Systematic reviews (SRs) in 2000 to 2021, and primary studies in 2019 to 2021, on outcomes of supplemental screening modalities (digital breast tomography [DBT], MRI (full/abbreviated protocol), contrast enhanced mammography (CEM), ultrasound (hand-held [HHUS]/automated [ABUS]) in women with dense breasts (BI-RADS C&D) were identified. None of the SRs analyzed outcomes by cancer risk. Meta-analysis of the primary studies was not feasible due to lack of studies (MRI, CEM, DBT) or methodological heterogeneity (ultrasound); therefore, findings were summarized narratively. For average risk, a single MRI trial reported a superior screening performance (higher cancer detection rate [CDR] and lower interval cancer rate [ICR]) compared to HHUS, ABUS and DBT. For intermediate risk, ultrasound was the only modality assessed, but accuracy estimates ranged widely. For mixed risk, a single CEM study reported the highest CDR, but included a high proportion of women with intermediate risk. This systematic review does not allow a complete comparison of supplemental screening modalities for dense breast populations by breast cancer risk. However, the data suggest that MRI and CEM might generally offer superior screening performance versus other modalities. Further studies of screening modalities are urgently required., Competing Interests: Conflicts of interest The authors have no other conflicts of interest. Authors who are not employees of or consultants for the pharmaceutical industry (EM and GN) had control of inclusion of any data and information that might otherwise present a conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Many facets of tissue engineered models aim at understanding cellular mechanisms to recapitulate in vivo behavior, to study and mimic diseases for drug interventions, and to provide a better understanding toward improving regenerative medicine. Recent and rapid advances in stem cell biology, material science and engineering, have made the generation of complex engineered tissues much more attainable. One such tissue, human myocardium, is extremely intricate, with a number of different cell types. Recent studies have unraveled cardiac resident macrophages as a critical mediator for normal cardiac function. Macrophages within the heart exert phagocytosis and efferocytosis, facilitate electrical conduction, promote regeneration, and remove cardiac exophers to maintain homeostasis. These findings underpin the rationale of introducing macrophages to engineered heart tissue (EHT), to more aptly capitulate in vivo physiology. Despite the lack of studies using cardiac macrophages in vitro , there is enough evidence to accept that they will be key to making EHTs more physiologically relevant. In this review, we explore the rationale and feasibility of using macrophages as an additional cell source in engineered cardiac tissues. Impact statement Macrophages play a critical role in cardiac homeostasis and in disease. Over the past decade, we have come to understand the many vital roles played by cardiac resident macrophages in the heart, including immunosurveillance, regeneration, electrical conduction, and elimination of exophers. There is a need to improve our understanding of the resident macrophage population in the heart in vitro , to better recapitulate the myocardium through tissue engineered models. However, obtaining them in vitro remains a challenge. Here, we discuss the importance of cardiac resident macrophages and potential ways to obtain cardiac resident macrophages in vitro . Finally, we critically discuss their potential in realizing impactful in vitro models of cardiac tissue and their impact in the field.

Background: The King's College London Pre-hospital Care Programme (KCL PCP) is a student-run programme that provides undergraduate medical students with the opportunity to attend observer shifts with the local ambulance service. This study evaluates the contribution of pre-hospital exposure to medical students' clinical and professional development., Methods: Students were asked to complete a Likert-scale based survey on self-reported exposure and confidence in various aspects of acute patient assessment, communication and interprofessional education, both before and after the programme; additional qualitative questions querying their experience were asked post-programme. Pre and post-programme Likert-scale responses were matched and statistically analysed, alongside a thematic analysis of qualitative responses., Results: Exposure to ambulance service clinicians, confidence assessing acutely unwell patients, and confidence making clinical handovers all increased with statistical significance. Key areas of learning identified from the thematic analysis include increased confidence communicating with patients and families, and an enriched understanding of the work done by pre-hospital clinicians., Conclusions: Time spent in the pre-hospital environment shadowing ambulance service clinicians positively contributes to acute care knowledge, inter-personal skills and interprofessional understanding. Rotating medical students through the pre-hospital environment could bridge education gaps in these areas in a manner that complements traditional pre-clinical and clinical teaching.

The mycobacterium genus contains a broad range of species, including the human pathogens M. tuberculosis and M. leprae . These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Parker, Forrester, Kaldor, Dickerhof and Hampton.)

Background: Restraint is widely practised within inpatient mental health services and is considered a higher-risk procedure for patients and staff. There is a sparsity of evidence in respect of the efficacy of personal protective equipment (PPE) used during restraint for reducing risk of infection., Methods: A series of choreographed restraint episodes were used to simulate contact contamination in research participants playing the roles of staff members and a patient. For comparison, one episode of simulated recording of physical observations was taken. Ultraviolet (UV) fluorescent material was used to track the simulated contact contamination, with analysis undertaken using established image registration techniques of UV photographs. This was repeated for three separate sets of PPE., Results: All three PPE sets showed similar performance in protecting against contamination transfer. For teams not utilising coveralls, this was dependent upon effective cleansing as part of doffing. There were similar patterns of contamination for restraint team members assigned to specific roles, with hands and upper torso appearing to be higher-risk areas. The restraint-related contamination was 23 times higher than that observed for physical observations., Discussion: A second layer of clothing that can be removed showed efficacy in reducing contact contamination. PPE fit to individual is important. Post-restraint cleansing procedures are currently inadequate, with new procedures for face and neck cleansing required. These findings leave scope for staff to potentially improve their appearance when donning PPE and engaging with distressed patients.

Neutrophils are often the major leukocyte at sites of mycobacterial infection, yet little is known about their ability to kill mycobacteria. In this study we have investigated whether the potent antibacterial oxidant hypochlorous acid (HOCl) contributes to killing of Mycobacterium smegmatis when this bacterium is phagocytosed by human neutrophils. We found that M. smegmatis were ingested by neutrophils into intracellular phagosomes but were killed slowly. We measured a t 1/2 of 30 min for the survival of M. smegmatis inside neutrophils, which is 5 times longer than that reported for Staphylococcus aureus and 15 times longer than Escherichia coli Live-cell imaging indicated that neutrophils generated HOCl in phagosomes containing M. smegmatis ; however, inhibition of HOCl production did not alter the rate of bacterial killing. Also, the doses of HOCl that are likely to be produced inside phagosomes failed to kill isolated bacteria. Lethal doses of reagent HOCl caused oxidation of mycothiol, the main low-m.w. thiol in this bacterium. In contrast, phagocytosed M. smegmatis maintained their original level of reduced mycothiol. Collectively, these findings suggest that M. smegmatis can cope with the HOCl that is produced inside neutrophil phagosomes. A mycothiol-deficient mutant was killed by neutrophils at the same rate as wild-type bacteria, indicating that mycothiol itself is not the main driver of M. smegmatis resistance. Understanding how M. smegmatis avoids killing by phagosomal HOCl could provide new opportunities to sensitize pathogenic mycobacteria to destruction by the innate immune system., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Background & Aim: Following acetaminophen (APAP) overdose, acute liver injury (ALI) can occur in patients that present too late for N-acetylcysteine treatment, potentially leading to acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate immunological function and paracrine activity. Syngeneic primary bone marrow-derived macrophages (BMDMs) were tested as a cell-based therapy in a mouse model of APAP-induced ALI (APAP-ALI)., Methods: Several phenotypically distinct BMDM populations were delivered intravenously to APAP-ALI mice when hepatic necrosis was established, and then evaluated based on their effects on injury, inflammation, immunity, and regeneration. In vivo phagocytosis assays were used to interrogate the phenotype and function of alternatively activated BMDMs (AAMs) post-injection. Finally, primary human AAMs sourced from healthy volunteers were evaluated in immunocompetent APAP-ALI mice., Results: BMDMs rapidly localised to the liver and spleen within 4 h of administration. Injection of AAMs specifically reduced hepatocellular necrosis, HMGB1 translocation, and infiltrating neutrophils following APAP-ALI. AAM delivery also stimulated proliferation in hepatocytes and endothelium, and reduced levels of several circulating proinflammatory cytokines within 24 h. AAMs displayed a high phagocytic activity both in vitro and in injured liver tissue post-injection. Crosstalk with the host innate immune system was demonstrated by reduced infiltrating host Ly6C hi macrophages in AAM-treated mice. Importantly, therapeutic efficacy was partially recapitulated using clinical-grade primary human AAMs in immunocompetent APAP-ALI mice, underscoring the translational potential of these findings., Conclusion: We identify that AAMs have value as a cell-based therapy in an experimental model of APAP-ALI. Human AAMs warrant further evaluation as a potential cell-based therapy for APAP overdose patients with established liver injury., Lay Summary: After an overdose of acetaminophen (paracetamol), some patients present to hospital too late for the current antidote (N-acetylcysteine) to be effective. We tested whether macrophages, an injury-responsive leukocyte that can scavenge dead/dying cells, could serve as a cell-based therapy in an experimental model of acetaminophen overdose. Injection of alternatively activated macrophages rapidly reduced liver injury and reduced several mediators of inflammation. Macrophages show promise to serve as a potential cell-based therapy for acute liver injury., Competing Interests: Conflict of interest P.S.L., L.F., and S.J.F. have patents pending, entitled ‘Macrophage-based therapy’ in national territories of USA, Europe, Japan, China and Australia. These patents have been derived from PCT/GB2017/052769 filed 18/09/2017 and claim priority from UK application 1615923.8 filed 19/09/2016. Both of the original patents have now been abandoned because the original UK patent and PCT patent are no longer live and have now been replaced by the national patents. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Health care-associated infections are a common cause of patient morbidity and mortality. We sought to describe the trends in these infections in acute care hospitals, using data from 3 national point-prevalence surveys., Methods: The Canadian Nosocomial Infection Surveillance Program (CNISP) conducted descriptive point-prevalence surveys to assess the burden of health care-associated infections on a single day in February of 2002, 2009 and 2017. Surveyed infections included urinary tract infection, pneumonia, Clostridioides difficile infection, infection at surgical sites and bloodstream infections. We compared the prevalence of infection across the survey years and considered the contribution of antimicrobial-resistant organisms as a cause of these infections., Results: We surveyed 28 of 33 (response rate 84.8%) CNISP hospitals (6747 patients) in 2002, 39 of 55 (response rate 71.0%) hospitals (8902 patients) in 2009 and 47 of 66 (response rate 71.2%) hospitals (9929 patients) in 2017. The prevalence of patients with at least 1 health care-associated infection increased from 9.9% in 2002 (95% confidence interval [CI] 8.4%-11.5%) to 11.3% in 2009 (95% CI 9.4%-13.5%), and then declined to 7.9% in 2017 (95% CI 6.8%-9.0%). In 2017, device-associated infections accounted for 35.6% of all health care-associated infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 3.9% of all organisms identified from 2002 to 2017; other antibiotic-resistant organisms were uncommon causes of infection for all survey years., Interpretation: In CNISP hospitals, there was a decline in the prevalence of health care-associated infection in 2017 compared with previous surveys. However, strategies to prevent infections associated with medical devices should be developed. Apart from MRSA, few infections were caused by antibiotic-resistant organisms., Competing Interests: Competing interests: None declared., (© 2019 Joule Inc. or its licensors.)

Mast cells are tissue-resident immune cells. Their overgrowth/overactivation results in a range of common distressing, sometimes life-threatening disorders, including asthma, psoriasis, anaphylaxis, and mastocytosis. Currently, drug discovery is hampered by use of cancer-derived mast cell lines or primary cells. Cell lines provide low numbers of mature mast cells and are not representative of in vivo mast cells. Mast cell generation from blood/bone marrow gives poor reproducibility, requiring 8-12 weeks of culture. Here we report a method for the rapid/robust production of mast cells from pluripotent stem cells (PSCs). An advantageous Gata2Venus reporter enriches mast cells and progenitors as they differentiate from PSCs. Highly proliferative mouse mast cells and progenitors emerge after 2 weeks. This method is applicable for rapid human mast cell generation, and could enable the production of sufficient numbers of physiologically relevant human mast cells from patient induced PSCs for the study of mast cell-associated disorders and drug discovery., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)