Slide tracheoplasty for congenital tracheal stenosis: A systematic review.

INTRODUCTION: Slide tracheoplasty has become the gold standard surgery for congenital tracheal stenosis (CTS). This condition is rare and the surgery can be challenging and is performed by experienced surgeons in tertiary centers. A few reports involving relatively small cohorts have been published. The aim of this review is to evaluate the post-operative mortality and morbidity of pediatric slide tracheoplasty for CTS. METHODS: A systematic literature review was performed according to PRISMA guidelines. The Medline and EMBASE databases were screened using a search strategy defined in collaboration with a librarian. We included articles reporting the post-operative mortality rate of slide tracheoplasties for treatment of CTS in children, when at least 10 patients were included. RESULTS: A total of 932 articles were reviewed, and 15 studies were eligible with a total of 845 patients. The overall post-operative mortality rate was 9.3 %, and most deaths were airway related. The open revision surgery rate after surgery was 2.8 % and the endoscopic revision rate was 27.6 %. DISCUSSION: This study highlights key factors to consider before the surgery and helps anticipate post-operative follow-up considerations for children with CTS. Several factors were identified as predictors of mortality including young age, weight at the time of surgery and association with lung hypoplasia or aplasia. CONCLUSION: Although slide tracheoplasty has gained popularity in recent years due to better outcomes, it remains a major surgery with mortality risk and the need for multidisciplinary management.

"The genie is out of the bottle": a qualitative study on the impact of COVID-19 on continuing professional development.

BACKGROUND: The onset of the COVID-19 pandemic catalysed a monumental shift in the field of continuing professional development (CPD). Prior to this, the majority of CPD group-learning activities were offered in-person. However, the pandemic forced the field to quickly pivot towards more novel methods of learning and teaching in view of social distancing regulations. The purpose of this study was to obtain the perspectives of CPD leaders on the impact of the pandemic to elucidate trends, innovations, and potential future directions in the field. METHODS: Semi-structured interviews were conducted between April-September 2022 with 23 CPD leaders from Canada and the USA. Interviews were audio-recorded, transcribed, and de-identified. A thematic analysis approach was used to analyse the data and generate themes. RESULTS: Participants characterised COVID-19 as compelling widespread change in the field of CPD. From the interviews, researchers generated six themes pertaining to the impact of the pandemic on CPD: (1) necessity is the mother of innovation, (2) the paradox of flexibility and accessibility, (3) we're not going to unring the bell, (4) reimagining design and delivery, (5) creating an evaluative culture, and (6) a lifeline in times of turmoil. CONCLUSION: This qualitative study discusses the impact of the pandemic on the field of CPD and leaders' vision for the future. Despite innumerable challenges, the pandemic created opportunities to reform design and delivery. Our findings indicate a necessity to maintain an innovative culture to best support learners, to improve the healthcare system, and to prepare for future emergencies.

Vibrotactile spatial acuity on the back.

Vibrotactile feedback can be built into clothing such as vests. This means that often vibrotactile information is presented to the back. It is known that the back has a relatively low spatial acuity. Spatial acuity varies across different limbs and sometimes with different locations on a limb. These known anisotropies suggest that there might be systematic variations in vibrotactile spatial acuity for different areas of the back and also for different orientations (i.e. horizontal vs. vertical). Here we systematically measured spatial acuity in four areas of the back for both horizontal and vertical orientations. The results show no significant differences in spatial acuity for the back areas that were tested. Spatial acuity was, however, higher in the horizontal direction than in the vertical direction by roughly a factor of two. This means that when designing vibrotactile displays for the back the tactor density can be lower in the vertical direction than in the horizontal direction and density should be constant for different areas of the back.

Impact of Educational Activity Formats, Online or In-Person, on the Intention of Medical Specialists to Adopt a Clinical Behaviour: A Comparative Study.

COVID-19 accelerated continuing professional development (CPD) delivered online. We aimed to compare the impact of in-person versus online CPD courses on medical specialists' behavioural intentions and subsequent behaviour. In this comparative before-and-after study, medical specialists attended in-person courses on nine clinical topics. A second group attended an adapted online version of these courses. Behavioural intention and its psychosocial determinants were measured before and immediately after the courses. Behaviour change was measured six months later. Generalised estimating equation (GEE) models were used to compare the impact of course formats. A total of 82/206 in-person registrants (mean age: 52±10 years; 50% men) and 318/506 on-line registrants (mean age: 49±12 years; men: 63%) participated. Mean intention before in-person courses was 5.99±1.31 and 6.43±0.80 afterwards (average intention gain 0.44, CI: 0.16-0.74; p=0.003); mean intention before online courses was 5.53±1.62 and 5.98±1.40 afterwards (average intention gain of 0.45, CI: 0.30-0.58; p<0.0001). Difference in intention gain between groups was not statistically significant. Behaviour reported six months later was not significantly associated with post-course intention in either group. However, the intention difference increased significantly among those who said they had adopted the targeted behaviour (paired wilcoxon test: n = 40 and p-value=0.002) while it did not increase significantly in the group of those who had not adopted a targeted behaviour (paired wilcoxon test: n = 16 and p-value=0.223). In conclusion, the increase in intention of specialists after CPD courses was similar whether the course was in-person or online. Also, an increase in intention in both groups signalled more likelihood of adoption.

Analytical propagation model for underwater free-space optical communication through realistic levels of oceanic absorption and scattering.

Optical communications (OC) through water bodies is an attractive technology for a variety of applications. Thanks to current single-photon detection capabilities, OC receiver systems can reliably decode very weak transmitted signals. This is the regime where pulse position modulation is an ideal scheme. However, there has to be at least one photon that goes through the pupil of the fore optics and lands in the assigned time bin. We estimate the detectable photon budget as a function of range for propagation through ocean water, both open and coastal. We make realistic assumptions about the water's inherent optical properties, specifically, absorption and scattering coefficients, as well as the strong directionality of the scattering phase function for typical hydrosol populations. We adopt an analytical (hence very fast) path-integral small-angle solution of the radiative transfer equation for multiple forward-peaked scattering across intermediate to large optical distances. Integrals are performed both along the directly transmitted beam (whether or not it is still populated) and radially away from it. We use this modeling framework to estimate transmission of a 1 J pulse of 532 nm light through open ocean and coastal waters. Thresholds for single-photon detection per time bin are a few km and a few 100 m. These are indicative estimates that will be reduced in practice due to sensor noise, background light, turbulence, bubbles, and so on, to be included in future work.

Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity.

Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that miR-6236 is a bona fide miRNA that is secreted by ATMs during obesity. Global or myeloid cell-specific deletion of miR-6236 aggravates obesity-associated adipose tissue insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. miR-6236 augments adipocyte insulin sensitivity by inhibiting translation of negative regulators of insulin signaling, including PTEN. The human genome harbors a miR-6236 homolog that is highly expressed in the serum and adipose tissue of obese people. hsa-MIR-6236 expression negatively correlates with hyperglycemia and glucose intolerance, and positively correlates with insulin sensitivity. Together, our findings establish miR-6236 as an ATM-secreted miRNA that potentiates adipocyte insulin signaling and protects against metabolic dysfunction during obesity.

Resonance Frequency Analysis Identifies Implant- and Host-Related Factors Associated With Bone-Anchored Hearing Implant Stability.

HYPOTHESIS: Resonance frequency analysis (RFA) is a reliable, noninvasive method to assess the stability of bone-anchored hearing implants (BAHIs), although surgical-, implant-, and host-related factors can affect its outcome. BACKGROUND: BAHI plays an important role in restoring hearing function. However, implant- and host-related factors contribute to premature implant extrusion. To mitigate this, noninvasive methods to assess implant stability, along with a better understanding of factors contributing to BAHI failure, are needed. METHODS: We evaluated the utility of RFA to quantify implant stability in sawbone (bone mimicking material), 29 human cadaveric samples, and a prospective cohort of 29 pediatric and 27 adult participants, and identified factors associated with implant stability. To validate the use of RFA in BAHI, we compared RFA-derived implant stability quotient (ISQ) estimates to peak loads obtained from mechanical push-out testing. RESULTS: ISQ and peak loads were significantly correlated (Spearman rho = 0.48, p = 0.0088), and ISQ reliably predicted peak load up to 1 kN. We then showed that in cadaveric samples, abutment length, internal table bone volume, and donor age were significantly associated with implant stability. We validated findings in our prospective patient cohort and showed that minimally invasive Ponto surgery (MIPS; versus linear incision), longer implantation durations (>16 wk), older age (>25 yr), and shorter abutment lengths (≤10 mm) were associated with better implant stability. Finally, we characterized the short-term reproducibility of ISQ measurements in sawbone and patient implants. CONCLUSIONS: Together, our findings support the use of ISQ as a measure of implant stability and emphasize important considerations that impact implant stability, including surgical method, implant duration, age, and abutment lengths.

Endoscopic repair of tracheoesophageal fistulas: A contemporary multi-institutional case series and literature review.

OBJECTIVES: Recurrent and primary tracheoesophageal fistulas (TEFs) are a challenging surgical pathology to treat, as standard open surgical approaches are associated with high morbidity and mortality. As such, endoscopic modalities have gained interest as an alluring alternative, yet variable success rates have been reported in the literature. The aim of this study was to provide a contemporary update of the literature and describe our institutional experience with the bronchoscopic obliteration of recurrent and primary TEFs. METHODS: Retrospective chart review of all pediatric patients having undergone endoscopic TEF repair at two pediatric academic centers in Montreal, Canada and Lille, France between January 1, 2008 to December 31, 2020. RESULTS: 28 patients with TEFs (20 recurrent, 8 primary) underwent a total of 48 endoscopic procedures. TEF repair was performed under endoscopic guidance using various combinations of techniques, including fistula de-epithelialization (endoscopic brush, thulium laser, trichloroacetic acid-soaked pledgets or electrocautery), tissue adhesives, submucosal augmentation, esophageal clip and stenting. Successful closure was achieved in 16 patients (57 %), while 12 (43 %) required eventual open or thoracoscopic repair. The mean number of endoscopic procedures was 1.7. There were no major treatment-related complications such as pneumothorax, mediastinitis or death (mean follow-up 50.8 months). CONCLUSIONS: Endoscopic repair of recurrent or primary TEFs is a valuable component of our therapeutic armamentarium and may contribute to decreased surgical morbidity in this complex patient population. Families should be counselled that endoscopic results may be more modest than with open or thoracoscopic approaches, and multiple procedures may be required.

Prey can detect predators via electroreception in air.

Predators and prey benefit from detecting sensory cues of each other's presence. As they move through their environment, terrestrial animals accumulate electrostatic charge. Because electric charges exert forces at a distance, a prey animal could conceivably sense electrical forces to detect an approaching predator. Here, we report such a case of a terrestrial animal detecting its predators by electroreception. We show that predatory wasps are charged, thus emit electric fields, and that caterpillars respond to such fields with defensive behaviors. Furthermore, the mechanosensory setae of caterpillars are deflected by these electrostatic forces and are tuned to the wingbeat frequency of their insect predators. This ability unveils a dimension of the sensory interactions between prey and predators and is likely widespread among terrestrial animals.

Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males.

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males (n = 9) and females (n = 7) completed two experimental days. On day 1, participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency (P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone.

BACKGROUND: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression. METHODS: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis. FINDINGS: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone. INTERPRETATION: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer. FUNDING: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK.

Isometric Exercise Training and Arterial Hypertension: An Updated Review.

Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.

Mapping the differential impact of spontaneous and conversational laughter on brain and mind: an fMRI study in autism.

Spontaneous and conversational laughter are important socio-emotional communicative signals. Neuroimaging findings suggest that non-autistic people engage in mentalizing to understand the meaning behind conversational laughter. Autistic people may thus face specific challenges in processing conversational laughter, due to their mentalizing difficulties. Using fMRI, we explored neural differences during implicit processing of these two types of laughter. Autistic and non-autistic adults passively listened to funny words, followed by spontaneous laughter, conversational laughter, or noise-vocoded vocalizations. Behaviourally, words plus spontaneous laughter were rated as funnier than words plus conversational laughter, and the groups did not differ. However, neuroimaging results showed that non-autistic adults exhibited greater medial prefrontal cortex activation while listening to words plus conversational laughter, than words plus genuine laughter, while autistic adults showed no difference in medial prefrontal cortex activity between these two laughter types. Our findings suggest a crucial role for the medial prefrontal cortex in understanding socio-emotionally ambiguous laughter via mentalizing. Our study also highlights the possibility that autistic people may face challenges in understanding the essence of the laughter we frequently encounter in everyday life, especially in processing conversational laughter that carries complex meaning and social ambiguity, potentially leading to social vulnerability. Therefore, we advocate for clearer communication with autistic people.

Molecular diversity of black corals from the Saudi Arabian Red Sea: a first assessment.

Black corals occur as part of benthic assemblages from shallow to deep waters in all oceans. Despite the importance in many benthic ecosystems, where these act as biodiversity aggregators, antipatharians remain poorly studied, with 75% of the known species occurring below recreational SCUBA diving depth limits. Currently, information regarding the diversity and evolutionary history is limited, with most studies focusing on Hawaii and the South Pacific Ocean. Other regions of the world have received less attention, such as the Red Sea, where only two black coral families and four genera have been recorded. We provide the first analysis of the molecular diversity of black corals in the eastern Gulf of Aqaba and the northern and central Saudi Arabian Red Sea, based on a dataset of 161 antipatharian colonies collected down to 627 m deep. Based on specimen morphology, we ascribed our material to 11 genera belonging to 4 of the 7 known Antipatharia families, i.e. Antipathidae, Aphanipathidae, Myriopathidae and Schizopathidae. The genus level phylogeny of three intergenic mitochondrial regions, the trnW-IGR-nad2 (IgrW ), nad5-IGR-nad1 (IgrN ) and cox3-IGR-cox1 was reconstructed including previously published material. Overall, we recovered six molecular clades that included exclusively Red Sea sequences, with the highest diversity occurring at mesophotic depths. This study highlights that diversity of black corals in the Red Sea is much higher than previously known, with seven new generic records, suggesting that this basin may be a hotspot for antipatharian diversity as is known for other taxa. Our results recovered unresolved relationships within the order at the familial and generic levels. This emphasises the urgent need for an integration of genomic-wide data with a re-examination of informative morphological features necessary to revise the systematics of the order at all taxonomic levels.

Measurement of Water Uptake and States in Nafion Membranes Using Humidity-Controlled Terahertz Time-Domain Spectroscopy.

Perfluorinated sulfonic acid ionomers are well known for their unique water uptake properties and chemical/mechanical stability. Understanding their performance-stability trade-offs is key to realizing membranes with optimal properties. Terahertz time-domain spectroscopy has been demonstrated to resolve water states inside industrially relevant membranes, producing qualitatively agreeable results to conventional gravimetric analysis and prior demonstrations. Using the proposed humidity-controlled terahertz time-domain spectroscopy, here we quantify this detailed water information inside commercially available Nafion membranes at various humidities for direct comparison against literature values from dynamic vapor sorption, differential scanning calorimetry, and Fourier transform infrared spectroscopy on selected samples. Using this technique therefore opens up opportunities for rapid future parameter space investigation for membrane optimization.

Does socioeconomic and environmental burden affect vulnerability to extreme air pollution and heat? A case-crossover study of mortality in California.

BACKGROUND: Extreme heat and air pollution is associated with increased mortality. Recent evidence suggests the combined effects of both is greater than the effects of each individual exposure. Low neighborhood socioeconomic status ("socioeconomic burden") has also been associated with increased exposure and vulnerability to both heat and air pollution. We investigated if neighborhood socioeconomic burden or the combination of socioeconomic and environmental exposures ("socioenvironmental burden") modified the effect of combined exposure to extreme heat and particulate air pollution on mortality in California. METHODS: We used a time-stratified case-crossover design to assess the impact of daily exposure to extreme particulate matter <2.5 µm (PM2.5) and heat on cardiovascular, respiratory, and all-cause mortality in California 2014-2019. Daily average PM2.5 and maximum temperatures based on decedent's residential census tract were dichotomized as extreme or not. Census tract-level socioenvironmental and socioeconomic burden was assessed with the CalEnviroScreen (CES) score and a social deprivation index (SDI), and individual educational attainment was derived from death certificates. Conditional logistic regression was used to estimate associations of heat and PM2.5 with mortality with a product term used to evaluate effect measure modification. RESULTS: During the study period 1,514,292 all-cause deaths could be assigned residential exposures. Extreme heat and air pollution alone and combined were associated with increased mortality, matching prior reports. Decedents in census tracts with higher socioenvironmental and socioeconomic burden experienced more days with extreme PM2.5 exposure. However, we found no consistent effect measure modification by CES or SDI on combined or separate extreme heat and PM2.5 exposure on odds of total, cardiovascular or respiratory mortality. No effect measure modification was observed for individual education attainment. CONCLUSION: We did not find evidence that neighborhood socioenvironmental- or socioeconomic burden significantly influenced the individual or combined impact of extreme exposures to heat and PM2.5 on mortality in California. IMPACT: We investigated the effect measure modification by socioeconomic and socioenvironmental of the co-occurrence of heat and PM2.5, which adds support to the limited previous literature on effect measure modification by socioeconomic and socioenvironmental burden of heat alone and PM2.5 alone. We found no consistent effect measure modification by neighborhood socioenvironmental and socioeconomic burden or individual level SES of the mortality association with extreme heat and PM2.5 co-exposure. However, we did find increased number of days with extreme PM2.5 exposure in neighborhoods with high socioenvironmental and socioeconomic burden. We evaluated multiple area-level and an individual-level SES and socioenvironmental burden metrics, each estimating socioenvironmental factors differently, making our conclusion more robust.

Sex differences in muscle morphology between male and female sprinters.

There is a marked difference between males and females in sprint running performance, yet a comprehensive investigation of sex differences in the muscle morphology of sprinters, which could explain the performance differences, remains to be completed. This study compared muscle volumes of 23 individual leg muscles and 5 functional muscle groups, assessed with 3 T magnetic resonance imaging, between male (n = 31) and female (n = 22) sprinters, as well as subgroups of elite males (EM, n = 5), elite females (EF, n = 5), and performance-matched (to elite females) males (PMMEF, n = 6). Differences in muscle volume distribution between EM, EF, and unathletic male (UM) controls were also assessed. For the full cohorts, male sprinters were more muscular than their female counterparts, but the differences were nonuniform and anatomically variable, with the largest differences in the hip extensors and flexors. However, among elite sprinters the sex differences in the volume of the functional muscle groups were almost uniform (absolute volume +47-53%), and the muscle volume distribution of EM was more similar to EF than to UM (P < 0.039). For PMMEF, relative hip extensor volume, but not stature or percent body fat, differentiated for performance (PMMEF and EF < EM) rather than sex. In conclusion, although the full cohorts of sprinters showed a marked sex difference in the amount and distribution of muscle mass, elite sprinters appeared to be selected for a common muscle distribution phenotype that for these elite subgroups was a stronger effect than that of sex. Relative hip extensor muscle volume, rather than stature, percent body fat, or total relative muscle volume, appeared to be the primary determinant of the sex difference in performance.NEW & NOTEWORTHY We present novel evidence suggesting muscle volume, specifically relative hip extensor volume, may be a primary deterministic variable for the sex difference in sprint performance, such that with matched sprint times, male and female sprinters may be expected to have equivalent muscle morphology. We highlight striking similarities in distribution of leg muscle mass between elite male and female sprinters and provide evidence for the existence of a muscular distribution phenotype specific to elite sprinters, irrespective of sex.

Proximity proteomics reveals UCH-L1 as an essential regulator of NLRP3-mediated IL-1ß production in human macrophages and microglia.

Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex is an essential innate immune signaling mechanism. To reveal how human NLRP3 inflammasome assembly and activation are controlled, in particular by components of the ubiquitin system, proximity labeling, affinity purification, and RNAi screening approaches were performed. Our study provides an intricate time-resolved molecular map of different phases of NLRP3 inflammasome activation. Also, we show that ubiquitin C-terminal hydrolase 1 (UCH-L1) interacts with the NACHT domain of NLRP3. Downregulation of UCH-L1 decreases pro-interleukin-1ß (IL-1ß) levels. UCH-L1 chemical inhibition with small molecules interfered with NLRP3 puncta formation and ASC oligomerization, leading to altered IL-1ß cleavage and secretion, particularly in microglia cells, which exhibited elevated UCH-L1 expression as compared to monocytes/macrophages. Altogether, we profiled NLRP3 inflammasome activation dynamics and highlight UCH-L1 as an important modulator of NLRP3-mediated IL-1ß production, suggesting that a pharmacological inhibitor of UCH-L1 may decrease inflammation-associated pathologies.

Reduction of large vessel traffic improves water quality and alters fish habitat-use throughout a large river.

Rivers are increasingly used as superhighways for the continental-scale transportation of freight goods, but the ecological impact of large vessel traffic on river ecosystems is difficult to study. Recently, the temporary maintenance closure of lock and dam systems on the Illinois Waterway (USA) brought commercial vessel traffic to a halt along the river's length, offering a rare opportunity to study the response of the ecosystem before, during, and after an extended pause of this persistent anthropogenic disturbance. We observed improvements in main- and side-channel water quality and a redistribution of fish habitat-use during a months-long, near-complete reduction of large vessel traffic. Over 3600 water quality and 1300 fish community samples indicate that large vessel traffic reduction coincided with a 33 % reduction in turbidity as well as increased use of sampling strata near vessel navigation corridors by sound-sensitive and rheophilic fishes. Gizzard shad (Dorosoma cepedianum), the most abundant species in the system, also expanded their use of these 'impact' areas. Though inland waterway transport is an economically- and climate-friendly alternative to trucking and rail for the shipment of freight, our data suggest that intense vessel traffic may have profound physical and biological impacts across a large river. Monitoring and mitigation of ecological impacts of the ongoing expansion of inland waterway transport around the world will be critical to balancing large rivers as both useful navigation corridors and functional ecosystems.