Successful antibiotic stewardship in the electronic era.

A multi-faceted antimicrobial stewardship programme contributed to a 17.8% reduction in antibiotic consumption for our English NHS Trust. This dramatic achievement could be partially attributed to an empirical antibiotic guideline change, introduction of procalcitonin testing to guide in antibiotic decisions in SARS-CoV-2 inpatients and use of electronic antibiotic stewardship strategies. In this article, we describe the multifaceted, step-by-step antibiotic stewardship approach that weathered the SARS-CoV-2 pandemic and led to this dramatic improvement. Also included for completeness are interventions that did not pass the plan, do, study, act (PDSA) cycle and were therefore discontinued.

A contemporary survey of bumble bee diversity across the state of California.

Bumble bees (genus Bombus) are important pollinators with more than 260 species found worldwide, many of which are in decline. Twenty-five species occur in California with the highest species abundance and diversity found in coastal, northern, and montane regions. No recent studies have examined California bumble bee diversity across large spatial scales nor explored contemporary community composition patterns across the state. To fill these gaps, we collected 1740 bumble bee individuals, representing 17 species from 17 sites (~100 bees per site) in California, using an assemblage monitoring framework. This framework is intended to provide an accurate estimate of relative abundance of more common species without negatively impacting populations through overcollection. Our sites were distributed across six ecoregions, with an emphasis on those that historically hosted high bumble bee diversity. We compared bumble bee composition among these sites to provide a snapshot of California bumble bee biodiversity in a single year. Overall, the assemblage monitoring framework that we employed successfully captured estimated relative abundance of species for most sites, but not all. This shortcoming suggests that bumble bee biodiversity monitoring in California might require multiple monitoring approaches, including greater depth of sampling in some regions, given the variable patterns in bumble bee abundance and richness throughout the state. Our study sheds light on the current status of bumble bee diversity in California, identifies some areas where greater sampling effort and conservation action should be focused in the future, and performs the first assessment of an assembly monitoring framework for bumble bee communities in the state.

Body size variation in bees: regulation, mechanisms, and relationship to social organization.

Size polymorphism is common in bees, and is determined by environmental factors such as temperature, brood cell size, and the diet provided to developing larvae. In social bees, these factors are further influenced by intricate interactions between the queen, workers, and the developing brood which eventually determine the final size and caste of developing larvae. Environmental and social factors act in part on juvenile hormone and ecdysteroids, which are key hormonal regulators of body size and caste determination. In some social bees, body size variation is central for social organization because it structures reproductive division of labor, task allocation among workers, or both. At ecological scales, body size also impacts bee-mediated pollination services in solitary and social species by influencing floral visitation and pollination efficacy.

Managing Subdural Bleeding Associated With Rivaroxaban: A Series of 3 Cases.

OBJECTIVE: To report 3 cases of subdural bleeding associated with rivaroxaban managed by 3-factor prothrombin complex concentrate (PCC3). CASE SUMMARIES: Case 1 presented with a 1-cm thick subdural hematoma (SDH) 12 hours after her last dose of rivaroxaban. Case 2 presented with a right 1-cm acute right SDH with 2 to 3 mm of midline shift 24 hours after his last dose of rivaroxaban. Case 3 presented with a 1.8-cm thick right cerebral convexity hematoma 12 hours after her last dose of rivaroxaban. All patients received 23 to 35 units/kg PCC3 with 1 to 3 units of fresh frozen plasm (FFP) and demonstrated no progression in lesions measured by repeat computed tomography (CT). Two patients were discharged to rehabilitation facilities and 1 patient ultimately died due to the location of the lesion. DISCUSSION: Rivaroxaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and no clinical experience has been reported to date. These cases begin to illuminate differences among choices for managing bleeding associated with Xa inhibitors. CONCLUSION: In this case series, 25 to 35 units/kilogram PCC3 and FFP 1 to 3 units ceased rivaroxaban-associated bleeding without thrombogenic complications.

Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages.

The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of congenital and adult cardiac diseases. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart. Herein, we report the identification of isl1+ cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells represent authentic, endogenous cardiac progenitors (cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers (25%) in the absence of cell fusion, intact Ca2+-cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.

Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein.

The interleukin-6 cytokines, acting via gp130 receptor pathways, play a pivotal role in the reduction of cardiac injury induced by mechanical stress or ischemia and in promoting subsequent adaptive remodeling of the heart. We have now identified the small proline-rich repeat proteins (SPRR) 1A and 2A as downstream targets of gp130 signaling that are strongly induced in cardiomyocytes responding to biomechanical/ischemic stress. Upregulation of SPRR1A and 2A was markedly reduced in the gp130 cardiomyocyte-restricted knockout mice. In cardiomyocytes, MEK1/2 inhibitors prevented SPRR1A upregulation by gp130 cytokines. Furthermore, binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after CT-1 stimulation. Histological analysis revealed that SPRR1A induction after mechanical stress of pressure overload was restricted to myocytes surrounding piecemeal necrotic lesions. A similar expression pattern was found in postinfarcted rat hearts. Both in vitro and in vivo ectopic overexpression of SPRR1A protected cardiomyocytes against ischemic injury. Thus, this study identifies SPRR1A as a novel stress-inducible downstream mediator of gp130 cytokines in cardiomyocytes and documents its cardioprotective effect against ischemic stress.

The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury.

Enteroviral infections of the heart are among the most commonly identified causes of acute myocarditis in children and adults and have been implicated in dilated cardiomyopathy. Although there is considerable information regarding the cellular immune response in myocarditis, little is known about innate signaling mechanisms within the infected cardiac myocyte that contribute to the host defense against viral infection. Here we show the essential role of Janus kinase (JAK) signaling in cardiac myocyte antiviral defense and a negative role of an intrinsic JAK inhibitor, the suppressor of cytokine signaling (SOCS), in the early disease process. Cardiac myocyte-specific transgenic expression of SOCS1 inhibited enterovirus-induced signaling of JAK and the signal transducers and activators of transcription (STAT), with accompanying increases in viral replication, cardiomyopathy, and mortality in coxsackievirus-infected mice. Furthermore, the inhibition of SOCS in the cardiac myocyte through adeno-associated virus-mediated (AAV-mediated) expression of a dominant-negative SOCS1 increased the myocyte resistance to the acute cardiac injury caused by enteroviral infection. These results indicate that strategies directed at inhibition of SOCS in the heart and perhaps other organs can augment the host-cell antiviral system, thus preventing viral-mediated end-organ damage during the early stages of infection.