Interventions to Reduce Surgical Waste Burden: A Systematic Review.

Background: Operating suites are significant drivers of waste, pollution, and costs. Surgeons can help fight the climate crisis by implementing innovative strategies aimed at mitigating the environmental impact of surgical procedures and decreasing operational costs, and moving toward a more sustainable healthcare system. This study aims to review the literature describing interventions that reduce surgical waste. Methods: PubMed, Cochrane, and Embase were searched. Studies reporting interventions to reduce operative waste, including emissions, energy, trash, and other, were included. Case reports, opinion-based reports, reviews, and meta-analyses were excluded. Study quality was rated using MINORS and Jadad scales. Data were extracted from each study to calculate waste on a per case basis. Narrative review of studies was performed rather than meta-analysis. Results: The search yielded 675 unique hits, of which 13 (level of evidence: I-III) met inclusion criteria. Included studies were categorized by intervention type in relation to the operating and procedure room. Three studies evaluated provider education initiatives, three evaluated setup of instruments, two evaluated single-use items, four evaluated technique changes, and one evaluated surgical venue. Seven studies reported significant reductions in disposable surgical waste throughput, and seven reported significant reductions in cost. Conclusions: The results of this systemic review demonstrated the effectiveness of surgical waste reduction initiatives in reducing waste volume, cost, and carbon emissions. Within plastic surgery, minimal surgical packs resulted in reduced gross waste and cost while promoting patient satisfaction in hand surgery, supporting the continued development and implementation of such initiatives in a surgical context.

Thyrotoxic Periodic Paralysis in a Samoan Male With Metabolic Acidosis: A Case Report and Review of the Literature.

Thyrotoxic periodic paralysis (TPP) is a rare disorder characterized by muscle paralysis, thyrotoxicosis, and hypokalemia. It commonly manifests as paralysis of both proximal and distal upper and lower limbs, and if left untreated, may progress to respiratory failure or cardiac arrhythmias. It is most common in Asian males and is frequently precipitated by strenuous exercise, high carbohydrate diet, stress, corticosteroid therapy, or alcohol. Early diagnosis of TPP is crucial as the condition may be reversible with oral or IV potassium replacement therapy, and management of the underlying hyperthyroidism. We describe a Samoan man in his 30s who presented with acute onset lower extremity paralysis. Laboratory investigations revealed low serum potassium of 2.2 mEq/L (reference range 3.5-5.0 mEq/L) and thyrotoxicosis with a low (thyroid stimulating hormone (TSH) of <0.07 uIU/mL (reference range 0.27-4.20 uIU/mL) and an elevated free T4 of 5.4 ng/dL (reference range 0.9-2.1 ng/dL). He was treated with both oral and IV potassium chloride as well as propranolol and regained full strength in his extremities. While rare, TPP is a reversible complication of thyrotoxicosis and a high index of suspicion in clinical practice is essential to prevent adverse outcomes.

Patient-Reported Preoperative Depression as a Predictor of Psychosocial Outcomes After Gender-Affirming Facial Feminization Surgery.

OBJECTIVE: To understand psychosocial functioning before and after gender-affirming facial feminization surgery (FFS) as well as identify predictors of postoperative psychosocial functioning. SUMMARY BACKGROUND DATA: Few investigations have rigorously explored the impact of gender-affirming FFS on psychosocial functioning in transgender and gender non-binary (TGNB) individuals. This knowledge gap hinders the identification of methods to optimize mental health quality-of-life outcomes after FFS and carries repercussions for access to care. METHODS: Adult TGNB participants awaiting gender-affirming FFS were prospectively enrolled and administered Patient-Reported Outcomes Measurement Information System (PROMIS) instruments assessing anxiety, anger, depression, global mental and physical health, positive affect, emotional support, social isolation, companionship, and meaning and purpose before and 3-6 months after FFS. Paired t-tests compared pre- and postoperative scores. Multivariable linear models identified predictors of postoperative psychosocial outcomes. RESULTS: Among the domains, psychosocial scores improved for anxiety, depression, global mental health, social isolation, and positive affect after FFS. When accounting for potential variables contributing to postoperative psychosocial scores including other gender-affirming surgeries, hormone therapy duration, and private versus public insurance type, we found that preoperative depression scores independently predicted the variance in all other postoperative scores with global mental health (ß=-0.52, 95%CI -0.58--0.31 P<0.001), anxiety (ß=0.40, 95% CI 0.21-0.51, P<0.001), and meaning and purpose (ß=-0.52, 95% CI -0.78--0.42 P<0.001) as the strongest models. CONCLUSIONS: This study suggests that gender-affirming FFS improves psychosocial functioning; however, such improvements are highly influenced by the baseline psychological functioning of each individual. These findings indicate that preoperative psychological functioning may be a potential avenue for improving outcomes after FFS via perioperative psychological interventions.

Photon-efficient optical tweezers via wavefront shaping.

Optical tweezers enable noncontact trapping of microscale objects using light. It is not known how tightly it is possible to three-dimensionally (3D) trap microparticles with a given photon budget. Reaching this elusive limit would enable maximally stiff particle trapping for precision measurements on the nanoscale and photon-efficient tweezing of light-sensitive objects. Here, we customize the shape of light fields to suit specific particles, with the aim of optimizing trapping stiffness in 3D. We show, theoretically, that the confinement volume of microspheres held in sculpted optical traps can be reduced by one to two orders of magnitude. Experimentally, we use a wavefront shaping-inspired strategy to passively suppress the Brownian fluctuations of microspheres in every direction concurrently, demonstrating order-of-magnitude reductions in their confinement volumes. Our work paves the way toward the fundamental limits of optical control over the mesoscopic realm.

Single-frame transmission and phase imaging using off-axis holography with undetected photons.

Imaging with undetected photons relies upon nonlinear interferometry to extract the spatial image from an infrared probe beam and reveal it in the interference pattern of an easier-to-detect visible beam. Typically, the transmission and phase images are extracted using phase-shifting techniques and combining interferograms from multiple frames. Here we show that off-axis digital holography enables reconstruction of both transmission and phase images at the infrared wavelength from a single interferogram, and hence a single frame, recorded in the visible. This eliminates the need for phase stepping and multiple acquisitions, thereby greatly reducing total measurement time for imaging with long acquisition times at low flux or enabling video-rate imaging at higher flux. With this single-frame acquisition technique, we are able to reconstruct transmission images of an object in the infrared beam with a signal-to-noise ratio of 3.680 ± 0.004 at 10 frames per second, and record a dynamic scene in the infrared beam at 33 frames per second.

Outcomes of Near-Total and Subtotal Resection of Sporadic Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate tumor control and facial nerve outcomes after gross-total (GTR), near-total (NTR), and subtotal resection (STR) of sporadic vestibular schwannomas (VS). DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched in August 2021 through inception following PRISMA guidelines. REVIEW METHODS: English language articles reporting tumor control and facial nerve outcomes of adults (≥18 years) with NTR and STR of VS were evaluated. Study characteristics, demographics data, tumor characteristics, type of surgical intervention, and outcome measures on tumor control and facial nerve function were collected. Pooled relative risk (RR) estimates for tumor recurrence and facial nerve outcomes were calculated and stratified by extent of resection. RESULTS: From an initial search of 2504 articles, 48 studies were included in the analysis. When comparing 1108 patients who underwent NTR to 3349 patients with GTR, the pooled RR of recurrence in the NTR cohort was 2.94 (95% confidence interval [CI] 1.65-5.24, P = .0002). When comparing 1016 patients who underwent STR to 6171 patients with GTR, the pooled RR of recurrence in the STR cohort was 11.50 (95% CI 6.64-19.92, P < .0001). Estimates for risk of tumor regrowth for less-than-complete resection are presented. There was no elevated risk of adverse facial nerve outcome (defined as House-Brackmann grade III and above) in each category of extent of resection compared to GTR. CONCLUSION: Extent of resection predicts risk of tumor recurrence/regrowth following microsurgical resection. Favorable facial nerve outcome should be weighed against the increased risk of regrowth and the potential need for further treatment.

Interactive data exploration websites for large-scale electrophysiology.

Methodological advances in neuroscience have enabled the collection of massive datasets which demand innovative approaches for scientific communication. Existing platforms for data storage lack intuitive tools for data exploration, limiting our ability to interact effectively with these brain-wide datasets. We introduce two public websites: (Data and Atlas) developed for the International Brain Laboratory which provide access to millions of behavioral trials and hundreds of thousands of individual neurons. These interfaces allow users to discover both the raw and processed brain-wide data released by the IBL at the scale of the whole brain, individual sessions, trials, and neurons. By hosting these data interfaces as websites they are available cross-platform with no installation. By releasing each site's code as a modular open-source framework, other researchers can easily develop their own web interfaces and explore their own data. As neuroscience datasets continue to expand, customizable web interfaces offer a glimpse into a future of streamlined data exploration and act as blueprints for future tools.

Half-Inch Monolithic Spatial Heterodyne Raman Spectrometer: A Study of Polarized Raman Spectra of Organic Liquids and Instrumental Performance.

Raman spectroscopy allows for the unambiguous identification of materials through the inelastic scattering of light. This technique has a great many uses in various aspects of society from academic, scientific, and industry. This paper explores a specific type of Raman spectrometer called a spatial heterodyne Raman spectrometer (SHRSy), which is a variation of an interferometric spectrometer. It utilizes a Michelson interferometer and replaces the mirrors with gratings that transform it from a time-domain spectrometer to a spatial-domain spectrometer, allowing for the entirety of the spectrum to be captured at once. This study specifically tests a half-inch two-grating monolithic SHRS (½-in. 2g-mSHRS), which has a weight of <60 g and a size of 2.2 × 2.2 × 1.3 cm. To do this we excite a variety of organic liquids with a 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) pulsed laser, using an excitation energy of 6.5 mJ/pulse and distance of 3 m in conjunction with an intensified charge-coupled device camera. This is the first time that the SHRS has been used for investigating polarized Raman spectra of liquids. We discuss and contrast the instrumental properties such as resolution, spectral range, étendue, and field of view with previously tested mSHRS to give context to the instrument's performance.

Slow Fatigue and Highly Delayed Yielding via Shear Banding in Oscillatory Shear.

We study theoretically the dynamical process of yielding in cyclically sheared amorphous materials, within a thermal elastoplastic model and the soft glassy rheology model. Within both models we find an initially slow accumulation, over many cycles after the inception of shear, of low levels of damage in the form strain heterogeneity across the sample. This slow fatigue then suddenly gives way to catastrophic yielding and material failure. Strong strain localization in the form of shear banding is key to the failure mechanism. We characterize in detail the dependence of the number of cycles N^{*} before failure on the amplitude of imposed strain, the working temperature, and the degree to which the sample is annealed prior to shear. We discuss our finding with reference to existing experiments and particle simulations, and suggest new ones to test our predictions.

Point-of-care ultrasound is a useful adjunct tool to a clinician's assessment in the evaluation of severe hyponatraemia.

INTRODUCTION: Hyponatraemia is the most common electrolyte disorder in inpatients resulting mainly from an imbalance in water homeostasis. Intravascular fluid status assessment is pivotal but is often challenging given multimorbidity, polypharmacy and diuretics use. We evaluated the utility of point-of-care ultrasound (POCUS) as an adjunct tool to standard practice for fluid assessment in severe hyponatraemia patients. METHODS: Patients presenting with severe hyponatremia (Serum Sodium [Na] < 120 mmol/L; Normal range: 135-145 mol/L), managed by standard care were included. Hyponatraemia biochemistry work-up and POCUS examination were undertaken. Both clinician and POCUS independently assigned one of the three fluid status groups of hypovolaemia, hypervolaemia or euvolaemia. The final diagnosis of three fluid status groups at admission was made at the time of discharge by retrospective case review. Clinician's (standard of care) and POCUS fluid assessments were compared to that of the final diagnosis at the time of discharge. RESULTS: n = 19 patients were included. Median Na on admission was 113 mmol/L (109-116), improved to 129 ± 3 mmol/L on discharge. POCUS showed the higher degree of agreement with the final diagnosis (84%; n = 16/19), followed by the clinician (63%; n = 12/19). A trend towards higher accuracy of POCUS compared to clinician assessment of fluid status was noted (84% vs. 63%, p = 0.1611). Biochemistry was unreliable in 58% (n = 11/19) likely due to renal failure, polypharmacy or diuretic use. Inappropriate emergency fluid management was undertaken in 37% (n = 7/19) of cases based on initial clinician assessment. Thirst symptom correlated to hypovolaemia in 80% (4/5) cases. CONCLUSION: As subjective clinical and biochemistry assessments of fluid status are often unreliable due to co-morbidities and concurrent use of medications, POCUS can be a rapid objective diagnostic tool to assess fluid status in patients with severe hyponatraemia, to guide accurate emergency fluid management.

Load carriage physiology in normoxia and hypoxia.

PURPOSE: To determine the effects of load carriage in normoxia and normobaric hypoxia on ventilatory responses, hemodynamics, tissue oxygenation, and metabolism. METHODS: Healthy males (n = 12) completed 3 randomly ordered baseline graded exercise tests in the following conditions: (1) unloaded normoxic (U: FIO2 = 20.93%), (2) loaded (~ 30 kg) normoxic (LN), and (3) loaded hypoxic simulating ~ 3650 m (LH: FIO2 = ~ 13%). Thereafter, experimental exercise trials were completed in quasi-randomized order (i.e., U completed first) consisting of 3 × 10 min of walking (separated by 5 min seated rest) with stages matched with the U condition (in ascending order) for relative intensity, absolute oxygen consumption ([VO2]; 1.7 L min-1), and walking speed (1.45 ± 0.15 m s-1). RESULTS: Load carriage increased perceived exertion and reduced VO2max (LN: - 7%; LH: - 32%; p < 0.05). At matched VO2, stroke volume and tidal volume were reduced and maintained with LN and LH vs. U, respectively (p < 0.05). Increases in cardiac output and minute ventilation at matched VO2 (with LH) and speed (with LN and LH), were primarily accomplished via increases in heart rate and breathing frequency (p < 0.05). Cerebral oxygenated hemoglobin (O2HHb) was increased at all intensities with LN, but deoxygenated hemoglobin and total hemoglobin were increased with LH (p < 0.05). Muscle oxygen kinetics and substrate utilization were similar between LN and U, but LH increased CHO dependence and reduced muscle O2HHb at matched speed (p < 0.05). CONCLUSION: Load carriage reduces cardiorespiratory efficiency and increases physiological strain, particularly in hypoxic environments. Potential load carriage-induced alterations in cerebral blood flow may increase the risk for altitude illnesses and requires further study.

A large-scale experiment finds no consistent evidence of change in mortality or commercial productivity in silverlip pearl oysters (Pinctada maxima) exposed to a seismic source survey.

High-intensity, impulsive sounds are used to locate oil and gas reserves during seismic exploration of the seafloor. The impacts of this noise pollution on the health and mortality of marine invertebrates are not well known, including the silverlip pearl oyster (Pinctada maxima), which comprises one of the world's last remaining significant wildstock pearl oyster fisheries, in northwestern Australia. We exposed ≈11,000 P. maxima to a four-day experimental seismic survey, plus one vessel-control day. After exposure, survival rates were monitored throughout a full two-year production cycle, and the number and quality of pearls produced at harvest were assessed. Oysters from two groups, on one sampling day, exhibited reduced survival and pearl productivity compared to controls, but 14 other groups receiving similar or higher exposure levels did not. We therefore found no conclusive evidence of an impact of the seismic source survey on oyster mortality or pearl production.

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) and Sjögren Tool for Assessing Response (STAR) to B Cell-Targeted Therapy in the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS).

OBJECTIVE: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints. METHODS: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. RESULTS: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG. Furthermore, rituximab significantly down-regulated genes involved in immune-cell recruitment, lymphoid organization alongside antigen presentation, and T cell co-stimulatory pathways. In the peripheral compartment, rituximab down-regulated immunoglobulins  and auto-antibodies together with pro-inflammatory cytokines and chemokines. Interestingly, patients classified as responders  according to STAR displayed significantly higher baseline levels of C-X-C motif chemokine ligand-13 (CXCL13), interleukin (IL)-22, IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α), whereas a longitudinal analysis of serum T cell-related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS-responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ-receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. CONCLUSION: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification.

Global inventory of species categorized by known underwater sonifery.

A working group from the Global Library of Underwater Biological Sounds effort collaborated with the World Register of Marine Species (WoRMS) to create an inventory of species confirmed or expected to produce sound underwater. We used several existing inventories and additional literature searches to compile a dataset categorizing scientific knowledge of sonifery for 33,462 species and subspecies across marine mammals, other tetrapods, fishes, and invertebrates. We found 729 species documented as producing active and/or passive sounds under natural conditions, with another 21,911 species deemed likely to produce sounds based on evaluated taxonomic relationships. The dataset is available on both figshare and WoRMS where it can be regularly updated as new information becomes available. The data can also be integrated with other databases (e.g., SeaLifeBase, Global Biodiversity Information Facility) to advance future research on the distribution, evolution, ecology, management, and conservation of underwater soniferous species worldwide.

Single-Grating Monolithic Spatial Heterodyne Raman Spectrometer: An Investigation on the Effects of Detector Selection.

Spatial heterodyne Raman spectrometers (SHRSs) are modified forms of Michelson interferometers, except the mirrors in a Michelson interferometer are replaced with stationary diffraction gratings. This design removes the need for an entrance slit, as is the case in a dispersive spectrometer, and removes the need to scan the spectrum by using a moving mirror in a modern Michelson interferometer. In previous studies, various SHRS variants, such as free-standing two-grating SHRS, single-grating SHRS (1g-SHRS), monolithic SHRS (mSHRS), and single-grating mSHRS (1g-mSHRS), have been evaluated. However, the present study exclusively focuses on the 1g-mSHRS configuration. The 1g-mSHRS and 1g-SHRS increase the spectral range at fixed grating line density while trading off spectral resolution and resolving power. The mSHRS benefits from increased rigidity, lack of moving parts, and reduced footprint. In this study, we investigate how the choice of detector impacts the performance of the 1g-mSHRS system, with a specific focus on evaluating the performance of three types of cameras: charged-coupled device (CCD), intensified CCD (ICCD), and complementary metal-oxide-semiconductor (CMOS) cameras. These systems were evaluated using geological, organic, and inorganic samples using a 532 nm continuous wave laser for the CMOS and CCD cameras, and a 532 nm neodymium-doped yttrium aluminum garnet pulsed laser for the ICCD camera. The footprint of the 1g-mSHRS was 3.5 × 3.5 × 2.5 cm3 with a mass of 272 g or 80 g, depending on whether the monolith housing is included or not. We found that increasing the number of pixels utilized along the x-axis of the camera increases fringe visibility (FV) and optimizes the resolution (by capturing the entirety of the grating and magnifying the fringes). The number of pixels utilized in the y-axis, chip size, and dimensions, affect the signal-to-noise ratio of the systems. Additionally, we discuss the effect of pixel pitch on the recovery of Fizeau fringes, including the relationship between the Nyquist frequency, aliasing, and FV.

Gene Expression Within a Human Choroidal Neovascular Membrane Using Spatial Transcriptomics.

Purpose: Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process. Methods: To study how gene expression is altered in focal areas of pathology, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We performed differential expression to identify genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes. Results: Within the area of neovascularization, endothelial cells demonstrated increased expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we investigated regional gene expression patterns within the macular neural retina and between the macular and peripheral choroid. Conclusions: Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.

Therapeutic targets of fibrosis: Translational advances and current challenges.

In a physiological context, the extracellular matrix (ECM) provides an important scaffold for organs. Dysregulation of ECM in disease conditions, characterised by excess deposition of connective tissue and extracellular matrix in response to a pathological insult, is a key driver of disease progression in multiple organs. The resultant fibrosis is predominantly an irreversible process and directly contributes to, and exacerbates, dysfunction of an affected organ. This is particularly paramount in the kidney, liver, heart and lung. A hybrid Joint Meeting of NC-IUPHAR and British Pharmacological Society was held in Paris and via a webinar in November 2020, when two successive sessions were devoted to translational advances in fibrosis as a therapeutic target. On the upsurge of response to these sessions, the concept of a special themed issue on this topic emerged, and is entitled Translational Advances in Fibrosis as a Therapeutic Target. In this special issue, we seek to provide an up-to-date account of the diverse molecular mechanisms and causal role that fibrosis plays in disease progression (contributing to, and exacerbating, dysfunction of affected organs). Recent developments in the understanding of molecular targets involved in fibrosis, and how their actions can be manipulated therapeutically, are included. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.