Lack of Chemokine Signaling through CXCR5 Causes Increased Mortality, Ventricular Dilatation and Deranged Matrix during Cardiac Pressure Overload

RATIONALE: Inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), but a role for chemokines is largely unknown. Based on their role in inflammation and matrix remodeling in other tissues, we hypothesized that CXCL13 and CXCR5 could be involved in cardiac remodeling during HF. OBJECTIVE: We sought to analyze the role of the chemokine CXCL13 and its receptor CXCR5 in cardiac pathophysiology leading to HF. METHODS AND RESULTS: Mice harboring a systemic knockout of the CXCR5 (CXCR5(-/-)) displayed increased mortality during a follow-up of 80 days after aortic banding (AB). Following three weeks of AB, CXCR5(-/-) developed significant left ventricular (LV) dilatation compared to wild type (WT) mice. Microarray analysis revealed altered expression of several small leucine-rich proteoglycans (SLRPs) that bind to collagen and modulate fibril assembly. Protein levels of fibromodulin, decorin and lumican (all SLRPs) were significantly reduced in AB CXCR5(-/-) compared to AB WT mice. Electron microscopy revealed loosely packed extracellular matrix with individual collagen fibers and small networks of proteoglycans in AB CXCR5(-/-) mice. Addition of CXCL13 to cultured cardiac fibroblasts enhanced the expression of SLRPs. In patients with HF, we observed increased myocardial levels of CXCR5 and SLRPs, which was reversed following LV assist device treatment. CONCLUSIONS: Lack of CXCR5 leads to LV dilatation and increased mortality during pressure overload, possibly via lack of an increase in SLRPs. This study demonstrates a critical role of the chemokine CXCL13 and CXCR5 in survival and maintaining of cardiac structure upon pressure overload, by regulating proteoglycans essential for correct collagen assembly

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Biological monitoring as a valid tool to assess occupational exposure to mixtures of 2,4-:2,6-toluene diisocyanate

Background and Objectives: Despite its advantages over environmental monitoring, biological monitoring of exposure to 2,4-:2,6-toluene diisocyanate (TDI) mixtures is still underused. The present study was designed in order to evaluate the feasibility and reliability of biological monitoring in a factory producing polyurethane foam blocks. Methods: Airborne TDI isomers were sampled by both static and personal pumps and determined by HPLC with fluorimetric detection. Specific metabolites 2,4- and 2,6-toluenediamine (TDA) were determined by gas chromatography-mass spectrometry on hydrolysed urine samples collected from 16 workers at the beginning of the workweek and both before (BS) and at the end (ES) of the 4th workday. Additional samples were collected at the end of the 1st half-shift and at the beginning of the 2nd half-shift in 5 workers. Results: In the foam production shop, TDI values were on average about 20 μg/m3, with higher levels in the 2nd half-shift and peak levels in workers operating along the polymerization tunnel. Average TDI levels were significantly correlated with ES TDA concentrations (p<0.0001). TDA showed a fast urinary elimination phase leading to progressively higher TDA levels either during the shift (5 workers) and at the end-of-shift. A slower elimination phase with a weekly accumulation was demonstrated by values at the beginning of the workweek (higher than in unexposed subjects) and by their elevation in subsequent BS samples. Conclusions: The study demonstrates the feasibility and reliability of biological monitoring in workers exposed to 2,4-:2,6-TDI mixtures. This approach can provide information about both the daily and weekly exposure levels

The distribution and abundance of an island population of koalas (Phascolarctos cinereus) in the far north of their geographic range

Koalas are an iconic species of charismatic megafauna, of substantial social and conservation significance. They are widely distributed, often at low densities, and individuals can be difficult to detect, making population surveys challenging and costly. Consequently, koala population estimates have been limited and the results inconsistent. The aims of this study were to estimate the distribution, relative abundance and population size of the koalas on Magnetic Island, far north Queensland. Population densities were estimated in 18 different vegetation types present on the island using a Fecal Standing Crop Method. Koala density ranged from 0.404 ha−1, recorded in forest red gum and bloodwood woodland, to absence from eight of the vegetation types surveyed. The second highest density of 0.297 koalas ha−1 was recorded in mixed eucalypt woodland, which covers 45% of the island. The total abundance of koalas on Magnetic Island, not including those present in urban areas, was estimated at 825±175 (SEM). The large variation in koala density across vegetation types reinforces the need for sampling stratification when calculating abundance over large areas, as uniformity of habitat quality cannot be assumed. In this context, koala populations also occur in low densities in areas generally regarded as poor quality koala habitat. These results highlight the importance of protecting vegetation communities not traditionally considered to have high conservation value to koalas, as these habitats may be essential for maintaining viable, widespread, low-density populations. The results from this study provide a baseline to assess future trends in koala distribution, density and abundance on Magnetic Island

Changes in surgicaL behaviOrs dUring the CoviD-19 pandemic. The SICE CLOUD19 Study

BACKGROUND: The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic.METHODS: The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March-May 2020), II (June-September 2020), and III (October-December 2020).RESULTS: Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (>200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency (<20 procedures: 43.3%, 27.1%, 36.5% in the three phases, respectively) surgical activity. The use of laparoscopy also had a setback in phase I (25.8% performed less than 20% of elective procedures through laparoscopy). 60.6% of the respondents used a smoke evacuation device during laparoscopy in phase I, 61.6% in phase II, and 64.2% in phase III. Almost all responders (82.8% vs. 93.2% vs. 92.7%) in each analyzed period did not modify or reduce the use of high-energy devices.CONCLUSION: This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic