Timely intravenous (IV) to oral antimicrobial switch (IV-oral-switch) is a key antimicrobial stewardship (AMS) strategy. A retrospective audit was undertaken to determine concordance with IV-oral-switch guidelines in the context of a long-standing, tightly regulated AMS program. Data from 107 general medical and surgical patients in an Australian hospital were analysed. Median duration of IV antimicrobial courses before switching to oral therapy was 3 days (interquartile range, 2.25-5.00). Timely IV-oral-switch occurred in 57% (n=61) of patients. The median delay to switching was 0 days (IQR 0 to 1.25). In most courses (92/106, 86.8%), the choice of oral alternative after switching was appropriate. In 45% (47/105) of courses, total duration of therapy (IV plus oral) exceeded the recommended duration by >1.0 day. Excessive IV antimicrobial duration was uncommon at a hospital with a tightly regulated AMS program. Total duration of therapy was identified as an AMS target for improvement.

Introduction Left atrial posterior wall (LAPW) isolation may be performed as an additional atrial fibrillation (AF) ablation strategy based on pulmonary vein isolation. A modified posterior-inferior line (MPL) was proposed for reducing esophageal injury. The aim of this study was to evaluate the anatomical characteristics of the MPL, compared with the CPL. Methods and Results Multidetector computed tomography was performed in 102 consecutive AF patients (male/female = 60/42) preoperative, and the parameters were evaluated as follows: the distance from MPL and CPL to the esophagus, fat pad presence and thickness in the course of MPL and CPL, and the esophageal route below CPL. The average distance from the MPL to the esophagus was longer than from CPL to the esophagus (3.7 ± 1.5mm vs 1.7 ± 0.4mm, P < 0.001). Fat pad presence was higher in the course of MPL than CPL. The myocardium tissue and fat pad under MPL was thicker than under CPL (2.9 ± 1.1mm vs 1.6 ± 0.3mm, P < 0.001; 1.4 ± 0.6mm vs 0.9 ± 0.2mm, P < 0.001), respectively. In patients whose esophagus was unconfined in a triangular space at the left inferior pulmonary vein level, the average distance from MPL to esophagus was longer than the confined patients (4.0 ± 1.7mm vs 3.2 ± 1.0mm, P = 0.001). Conclusion The MPL was far away from the esophagus with thicker myocardium tissue and more fat pad than the CPL; thus, MPL could serve as a favorable alternative in linear ablation for LAPW isolation.

AIM: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to eradicate respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications of both treatment and prophylaxis. METHODS: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. RESULTS: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long. CONCLUSIONS: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.

Despite widespread evidence that biological invasion influences both the biotic and abiotic soil environments, the extent to which these two pathways underpin the effects of invasion on plant traits and performance is unknown. Leveraging a long-term (14-yr) field experiment, we show that an allelochemical-producing invader affects plants through biotic mechanisms, altering the soil fungal community composition, with no apparent shifts in soil nutrient availability. Changes in belowground fungal communities result in high costs of nutrient uptake for native perennials and a shift in functional traits linked to their water and nutrient use efficiencies. Some species in the invaded community compensate for high nutrient costs by reducing nutrient uptake and maintaining photosynthesis by expending more water, which demonstrates a trade-off in trait investment. For the first time, we show that the disruption of belowground nutritional symbionts can drive native plants toward novel regions in order to maintain their water and nutrient economics.

We present the CT angiogram images of a 43 year old lady with an isolated single coronary artery arising from the noncoronary sinus with a narrow slit like orifice and oblique take off.

The evolutionary histories of alpine species are often directly associated with responses to glaciation. Deep divergence among populations and complex patterns of genetic variation have been inferred as consequences of persistence within glacier boundaries (i.e. on nunataks), while shallow divergence and limited genetic variation is assumed to result from expansion from large refugia at the edge of ice shields (i.e. massifs de refuge). However, for some species, dependence on specific microhabitats could profoundly influence their spatial and demographic response to glaciation, and such a simple dichotomy may obscure the localization of actual refugia. In this study, we use the Nebria ingens complex (Coleoptera: Carabidae), a water-affiliated ground beetle lineage, to test how drainage basins are linked to their observed population structure. By analyzing mitochondrial COI gene sequences and genome-wide single nucleotide polymorphisms, we find that the major drainage systems of the Sierra Nevada Mountains in California best explain the population structure of the N. ingens complex. In addition, we find that an intermediate morphotype within the N. ingens complex is the product of historical hybridization of N. riversi and N. ingens in the San Joaquin basin during glaciation. This study highlights the importance of considering ecological preferences in how species respond to climate fluctuations and provides an explanation for discordances that are often observed in comparative phylogeographic studies.

Rationale: Aerosolized albuterol is widely used, but its safety and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established. Objectives: To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD. Methods: Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25mg, 2.5mg) and 3ml of normal saline were administered every 4 hours during separate 24-hour treatment periods assigned in random order with a 6-hour washout phase between periods. The primary outcome was the absolute change (post–pre therapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia. Results: Average within subject EF75 values improved with each therapy: saline placebo (+0.45L/min  2.5, p=0.04), 1.25mg of albuterol (+0.70L/min  2.4, p<0.001), and 2.5mg of albuterol (+0.38L/min  2.4, p=0.06). However, 1.25mg of albuterol (0.26L/min; 95% CI -0.19, 0.72) and 2.5mg (-0.10L/min; 95% CI -0.77, 0.57) produced similar changes in EF75 when compared to saline. All secondary outcomes were similar between saline and 1.25mg of albuterol. Peak inspiratory pressure needed to deliver goal tidal volumes (7.5% relative decrease, 95% CI 2.6, 12.3) and heart rate (6.5% increase, 95% CI 2.2, 10.8) differed significantly between albuterol 2.5mg and saline. Conclusion: Albuterol at 1.25mg and 2.5mg, compared to aerosolized saline, did not affect EF75 in infants with sBPD receiving invasive ventilation. Greater improvement in inspiratory pressures with albuterol 2.5mg suggests benefit, but close heart monitoring is indicated.

Silk fibroin (SF) from Bombyx mori has superior properties as both a textile and a biomaterial, and has been used to functionalize the surfaces of various medical inorganic materials including titanium (Ti). In this paper, we endowed SF with reversible binding ability to Ti by embedding a titanium binding motif (minTBP-1, RKLPDA). Artificial SF proteins were first created by conjugating gene cassettes for SF motif (AGSGAG) and minTBP-1 motif with different ratios, which have been shown to bind reversibly to Ti surfaces in quartz crystal microbalance analyses. Based on these results, the functionalized SF (TiBP-SF) containing the designed peptide [TS[(AGSGAG)3AS]2RKLPDAS]8 was prepared from the cocoon of transgenic B. mori, which accelerates the ossific differentiation of MC3T3-E1 cells when coated on titanium substrates. Thus, TiBP-SF presents an alternative for endowing the surfaces of titanium materials with osseointegration functionality, which would allow the exploration of potential applications in the medical field.

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Background: Several factors affect the long-term outcome of Fontan procedure, but a high pulmonary artery pressure is still one of the most important limitation for proceeding to a Fontan circulation. Herein, we present our experience in Fontan patients with high preoperative pulmonary artery pressures. Methods: A retrospective analysis was performed in order to evaluate Fontan patients with a preoperative pulmonary artery pressure > 15 mmHg between 2009 and 2020. Sixteen patients were operated on with a mean preoperative pulmonary artery pressure of 17.5 ± 2.1 mmHg. Results: Mean age at the time of Fontan procedure was 7.8 ± 5.6 years. All of the patients had stage II cavopulmonary anastomosis prior to Fontan completion, with a mean interstage period of 4 ± 2.6 years. Fontan completion was achieved with a polytetrafluorethylene (PTFE) tubular conduit, two of which were intra-extracardiac. Fenestration was performed in 4 (25%) cases. Postoperative pulmonary artery pressures and arterial oxygen saturation levels were 11.2 ± 2.8 mmHg and 97.8 ± 2, respectively. Mean duration of pleural drainage was 3.9 ± 5.3 days. Any morbidity and mortality were not encountered during a mean follow up period of 4.8 ± 7.7 years. Conclusions: The mid-term results of stage III Fontan completion in patients with pulmonary artery >15 mmHg are encouraging. Pulmonary vascular resistance, not only pulmonary artery pressure may help to identify high risk patients before Fontan completion.

The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019, presumed from the city of Wuhan, Hubei province in China and the subsequent declaration of the disease as a pandemic by the World Health Organization (WHO) as COVID-19 in March 2020, had significant impact on health care systems globally. Each country responded to this disease in different ways but broadly by fortifying and prioritising health care provision as well as introducing social lockdown aiming to contain the infection and minimizing the risk of transmission. In the United Kingdom, a lockdown was introduced by the government on 23rd of March 2020 and all health care services were focussed to challenge the impact of COVID-19. To do so, the United Kingdom National Health Service had to undergo widespread service reconfigurations and the so-called “Nightingale Hospitals” were created de novo to bolster bed provision and industries were asked to direct efforts to the production of ventilators. A government led public health campaign was publicised under the slogan of: “Stay home, Protect the NHS (National Health Service), Save lives”. The approach had a significant impact on delivery of all surgical services but particularly cardiac surgery with its inherent critical care bed capacity. This paper describes the impact on provision for elective and emergency cardiac surgery in the United Kingdom, with a focus on Aorto-vascular disease. We describe our Aorto-vascular activity and outcomes during the period of UK lockdown and present a patient survey of attitudes to aortic surgery during COVID-19 pandemic.

Duchene muscular dystrophies (DMD) is a rare but devastating disease resulting in progressive loss of ambulation, respiratory failure, DMD-associated cardiomyopathy (DMD-CM) and premature death. The use of corticosteroid and supportive respiratory care has improved outcomes, such that DMD-CM is now the leading cause of death. Historically, most programs have focused on the skeletal myopathy with less attention to the cardiac phenotype. This omission is rather astonishing since boys with DMD possess an absolute genetic risk of developing cardiomyopathy. Unfortunately, heart failure signs and symptoms are vague due to skeletal muscle myopathy leading to limited ambulation and traditional assessment of cardiac symptoms by the New York Heart Association classification is of limited utility even in advance stages. Echocardiographic assessment can detect cardiac dysfunction late in the disease course, but this has proven to be a poor surrogate marker of early cardiovascular disease and an inadequate predictor of DMD-CM. Indeed, one explanation for the paucity of cardiac therapeutic trials for DMD-CM has been the lack of a suitable end-point. Improve outcomes requires a better proactive treatment strategy, however the barrier to treatment is lack of a sensitive and specific tool to assess efficacy of treatment. The use of cardiac imaging has evolve from echocardiography to cardiac magnetic resonance imaging to assess cardiac performance. The purpose of this article is to review the role of cardiac imaging in characterizing the cardiac natural history of DMD-CM, highlighting the prognostic implications and an outlook on how this field might evolve in the future.

Abstract: This treatment describes the details of a methodical three step algorithm for determining the optimal operating conditions for the recrystallization separations of solid mixtures. Our algorithm was applied to optimally separate a representative pharmaceutical product (Caffeine) from a related pharmaceutical product (Theophylline). The limitations of such calculations with currently available, widely used predictive methods for computing solution thermodynamics without experimental data are directly examined. Also presented here is a novel two stage recrystallization procedure which can potentially dramatically improve the recovery yields of the desired products. The systematic optimization calculations described herein should enable researchers to quickly screen many potential solvent systems and operating conditions and concentrate experimental efforts only on the most promising candidates for such purifications.

Background: Despite recent advancements in prevention, treatment, and management options, cardiovascular diseases contribute to one of the leading causes of morbidity and mortality. Several studies highlight the compelling evidence for the existence of healthcare inequities and disparities in the treatment and management control of cardiovascular diseases. Aims: To explore the role of racial disparities in the treatment of various cardiovascular diseases, highlighting the role of socioeconomic and cultural factors, and ultimately postulate solutions to eliminate the disparities. Methods: A comprehensive review of literature was conducted using appropriate keywords on search engines of SCOPUS, Wiley, PubMed, and SAGE Journals. Conclusion: By continued research to eliminate healthcare inequalities, there exists a potential to improve health-related outcomes in minority populations.

1. In many social species, reproductive success varies between individuals within a population, resulting in socially structured populations. Social network analyses of familial relationships may provide insights on how fitness influences population-level demographic patterns. These methods have however rarely been applied to genetically-derived pedigree data from wild populations. 2. Here we use social networks to reconstruct parent-offspring relationships and create a familial network from polygamous boreal woodland caribou (Rangifer tarandus caribou) in Saskatchewan, Canada, to inform recovery efforts. We collected samples from 933 individuals at 15 variable microsatellite loci along with caribou-specific primers for sex identification. Using social network metrics, we assess the contribution of individual caribou to the population with several centrality metrics and then determine which metrics are best suited to inform on the population demographic structure. We look at the centrality of individuals from eighteen different local areas, along with the entire population. 3. We found substantial differences in centrality of individuals in different local areas, that in turn contributed differently to the full network, highlighting the importance of analyzing social networks at different scales. The full network revealed that boreal caribou in Saskatchewan form a complex, interconnected social network with strong familial ties, as the removal of edges with high betweenness did not result in distinct subgroups. Alpha, betweenness, and eccentricity centrality were the most informative metrics to characterize the population demographic structure and for spatially identifying areas of highest fitness levels and social cohesion across the range. 4. Synthesis and applications: Our results demonstrate the value of different network metrics in assessing genetically-derived familial networks. The spatial application of the familial networks identified areas of higher fitness levels and social cohesion across the range in support of population monitoring and recovery efforts.

Alcohol dehydrogenases (ADHs) play key roles in the production of various chemical precursors that are essential in pharmaceutical and fine chemical industries. To achieve practical application of ADHs in industrial processes, tailoring enzyme properties through rational design or directed evolution is often required. Here, we developed a secretion-based dual fluorescence assay (SDFA) for high-throughput screening of ADHs. In SDFA, an ADH of interest is fused to a mutated superfolder green fluorescence protein (MsfGFP), which could result in secretion of the fusion protein to culture broth. After a simple centrifugation step to remove the cells, the supernatant can be directly used to measure activity of the ADH based on a red fluorescence signal, whose increase is coupled to formation of NADH (a redox co-factor of ADHs) in the reaction. SDFA allows easy quantification of ADH concentration based on the green fluorescence signal of MsfGFP. This feature is useful in determining specific activity and may improve screening accuracy. Out of five ADHs we have tested with SDFA, four ADHs can be secreted and characterized. We successfully screened a combinatorial library of an ADH from Pichia finlandica and identified a variant with a 197-fold higher kcat/km value toward (S)-2-octanol compared to its wild-type.

Biotechnological application of multiple enzymes in different phases for target compounds synthesis poses a significant challenge for industrial process development. At the same time, a growing demand for natural flavors and fragrances opens up possibilities for novel biotechnological processes to replace current chemical synthesis routes, with additional advantages such as avoiding harsh reaction conditions and toxic chemicals, and less by-products in the system. Within complex biotechnological processes, the key for unfolding their industrial application potential in bioprocess engineering lies in their mathematical modeling. In this contribution, a multi-enzyme cascade reaction in a two-phase system implemented in a miniplant-scale reactor setup is mathematically modeled for the example of the flavoring agent cinnamyl cinnamate. Using our validated model and a mathematical optimization tool based on a genetic algorithm, optimization runs are performed to demonstrate the potential of computer-aided process development for complex biotechnological processes.

High performance thin-film composite (TFC) hollow fiber membranes have been developed for pervaporation dehydration by second interfacial polymerization (SIP) modification with 3 kinds of amine-functionalized β-cyclodextrin (amine-CDs), which were synthesized by modifying β-CD with ammonia, ethylenediamine (EDA) and tris(2-aminoethyl)amine, respectively. The chemical properties of amine-CDs and SIP-modified TFC membranes were characterized by various techniques. The effects of amine-CD type and SIP parameters (pH or concentration of CD-EDA solution) were studied systematically to acquire the optimized selective layer of TFC membranes for ethanol dehydration. Among all SIP-modified TFC membranes, the one with SIP by 2 wt% CD-EDA aqueous solution (pH=2) exhibited the most outstanding separation performance with a ultra-high permeation flux (3018.0±12.0 g/m2.h) and permeate concentration (98.7±0.2 wt% water) at 50 °C (equivalent to separation factor of 415), contributed by the effectively incorporated CD with rich hydrophilic functional groups and intrinsic nanocavities facilitating the passage of water molecules.