Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma.

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.

Matrix metalloproteinase 9: An emerging biomarker for classification of adherent vestibular schwannoma.

Background: The progression of vestibular schwannoma (VS) is intricately linked with interactions between schwannoma cells and the extracellular matrix. Surgical resection of VS is associated with substantial risks as tumors are adherent to the brainstem and cranial nerves. We evaluate the role of matrix metalloproteinase 9 (MMP9) in VS and explore its potential as a biomarker to classify adherent VS. Methods: Transcriptomic analysis of a murine schwannoma allograft model and immunohistochemical analysis of 17 human VS were performed. MMP9 abundance was assessed in mouse and human schwannoma cell lines. Transwell studies were performed to evaluate the effect of MMP9 on schwannoma invasion in vitro. Plasma biomarkers were identified from a multiplexed proteomic analysis in 45 prospective VS patients and validated in primary culture. The therapeutic efficacy of MMP9 inhibition was evaluated in a mouse schwannoma model. Results: MMP9 was the most highly upregulated protease in mouse schwannomas and was significantly enriched in adherent VS, particularly around tumor vasculature. High levels of MMP9 were found in plasma of patients with adherent VS. MMP9 outperformed clinical and radiographic variables to classify adherent VS with outstanding discriminatory ability. Human schwannoma cells secreted MMP9 in response to TNF-α which promoted cellular invasion and adhesion protein expression in vitro. Lastly, MMP9 inhibition decreased mouse schwannoma growth in vivo. Conclusions: We identify MMP9 as a preoperative biomarker to classify adherent VS. MMP9 may represent a new therapeutic target in adherent VS associated with poor surgical outcomes that lack other viable treatment options.

Topography-driven microclimate gradients shape forest structure, diversity, and composition in a temperate refugial forest.

Macroclimate drives vegetation distributions, but fine-scale topographic variation can generate microclimate refugia for plant persistence in unsuitable areas. However, we lack quantitative descriptions of topography-driven microclimatic variation and how it shapes forest structure, diversity, and composition. We hypothesized that topographic variation and the presence of the forest overstory cause spatiotemporal microclimate variation affecting tree performance, causing forest structure, diversity, and composition to vary with topography and microclimate, and topography and the overstory to buffer microclimate. In a 20.2-ha inventory plot in the North American Great Plains, we censused woody stems ≥1 cm in diameter and collected detailed topographic and microclimatic data. Across 59-m of elevation, microclimate covaried with topography to create a sharp desiccation gradient, and topography and the overstory buffered understory microclimate. The magnitude of microclimatic variation mirrored that of regional-scale variation: with increasing elevation, there was a decrease in soil moisture corresponding to the difference across ~2.1° of longitude along the east-to-west aridity gradient and an increase in air temperature corresponding to the difference across ~2.7° of latitude along the north-to-south gradient. More complex forest structure and higher diversity occurred in moister, less-exposed habitats, and species occupied distinct topographic niches. Our study demonstrates how topographic and microclimatic gradients structure forests in putative climate-change refugia, by revealing ecological processes enabling populations to be maintained during periods of unfavorable macroclimate.

Potential for a minor pine bark beetle pest, Dendroctonus terebrans (Coleoptera: Curculionidae: Scolytinae), to mediate host location by a major pine killer, Dendroctonus frontalis.

The southern pine beetle, Dendroctonus frontalis Zimmermann is an important mortality agent of Pinus in the eastern United States of America where it commonly shares hosts with the black turpentine beetle, Dendroctonus terebrans (Olivier), which infrequently kills trees. Unlike D. frontalis, which must kill its hosts to become established in the bark and reproduce, D. terebrans can occupy living hosts as a parasite. Olfactory mechanisms whereby D. frontalis initially locates hosts have not been demonstrated, whereas D. terebrans responds strongly to host odors. Because D. terebrans produces frontalin, the primary aggregation pheromone component for D. frontalis, and commonly arrives on hosts prior to D. frontalis, it has been hypothesized that D. terebrans pheromone components can mediate D. frontalis location of suitable, living trees. We assessed this possibility with studies of the semiochemical interactions between D. frontalis and D. terebrans. Coupled gas chromatography-electroantennographic detection analyses indicated that D. terebrans produces nine different olfactory stimulants for D. frontalis, nearly all of them known semiochemicals for D. frontalis. A trapping experiment designed to address the potentially confounding influence of lure contamination confirmed that the D. terebrans pheromone component exo-brevicomin enhances attraction of D. frontalis and thus could be an attractive kairomone. In ambulatory bioassays, male D. frontalis were strongly attracted to odors of frass of solitary female and paired D. terebrans, indicating their attraction to the naturally occurring semiochemicals of D. terebrans. Cues from D. terebrans may influence host and mate-finding success of D. frontalis and, thereby, the latter's virulence.

Postoperative Care and Outcomes in Solid-Organ Transplant Patients Undergoing Lower Extremity Fracture Treatment.

OBJECTIVES: To determine the postoperative outcomes in solid-organ transplant (SOT) patients undergoing operative treatment of lower extremity fractures. DESIGN: Retrospective comparative study. SETTING: Academic Level 1 trauma center. PATIENT SELECTION CRITERIA: Patients who underwent SOT and operative treatment of lower extremity fracture from 2013 to 2021 were identified, excluding pathologic fractures. OUTCOME MEASURES AND COMPARISONS: Postoperative complications, length of stay, time to death, 90-day and 1-year readmission rates, readmission causes, discharge location, and immunosuppressive regiments. RESULTS: Sixty-one patients with an average age of 67 years (range 29-88) were included. The mortality rate was 37.7%. The average follow-up was 15.2 months (range of 2 weeks-10 years). The majority of patients (32.8%) had received a liver transplant, and femoral neck fractures constituted the largest fracture group. The average length of stay was 10 days, with the shortest being 1 day and the longest being 126 days (SD 18). The majority of patients (57.3%) were not discharged home. Only 2 suffered from a postoperative complication requiring another procedure: hardware removal and liner exchange for periprosthetic joint infection, respectively. There was a 27.9% 90-day readmission rate with 2 deaths within that period with the most common being altered mental status (29.4%), genitourinary infections (17.6%), repeat falls (11.8%), and low hemoglobin requiring transfusion (11.8%). The longest average time to death analyzed by transplant type was found among lung transplant patients (1076 days, 62.5% mortality), followed by liver transplant patients (949 days, 35.0% mortality), and then kidney transplant patients (834 days, 38.9% mortality). The shortest time to death was 71 days from index procedure. CONCLUSIONS: Family members of SOT patients undergoing operative treatment of lower extremity fractures should be made aware of the high risk for 90-day readmission postoperatively (27.9%) and overall mortality (12.5%). Providers should be aware of the need for multidisciplinary involvement for inpatient care, monitoring postoperative complications, and facilitating discharge planning. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Identifying Tumor Microenvironment Biomarkers in Adherent and Cystic Vestibular Schwannomas.

OBJECTIVE: A subset of vestibular schwannomas (VSs), including cystic tumors, have higher postoperative morbidity because of the presence of adhesions between the tumor, facial nerve (FN), and brainstem. We identify tumor microenvironment (TME) biomarkers to better classify these tumors and predict the degree of tumor adherence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary skull base referral center. METHODS: Adult patients with cystic and solid VS matched in tumor size who underwent surgical resection were included. Expressions of seven biomarkers of extracellular matrix remodeling and tumor immune response were quantified via immunohistochemistry. The distribution of CD45+ immune cells was evaluated in intratumoral and perivascular compartments. The degree of tumor adherence was categorized as none, adherent to FN, or adherent to both FN and brainstem. RESULTS: Twenty-eight patients were included. Cystic VSs were significantly more adherent than solid VSs ( p = 0.02). Patients with adherent VS had shorter duration of symptoms and were more likely to undergo subtotal resection. In solid tumors, matrix metalloproteinase (MMP)-2 expression ( p = 0.02) and CD163+ macrophage infiltration ( p = 0.007) were correlated with tumor size. Linear discriminant analyses (LDAs) demonstrated MMP-2, MMP-14, CD80, CD163, and perivascular CD45 to be individually predictive of the degree of tumor adherence (all p < 0.05), with perivascular CD45 being the best independent predictor ( p = 0.005). An LDA model including these biomarkers demonstrated 100% accurate discrimination of all three levels of tumor adherence ( p = 0.04). CONCLUSIONS: Adherent VS have a distinct proinflammatory TME characterized by elevated MMP expression, enrichment of tumor-associated macrophages, and perivascular immune cell infiltration.

The societal economic impact of vision impairment in adults 40 years and above: findings from the National Eye Survey of Trinidad and Tobago.

BACKGROUND: Understanding and mitigating the societal economic impact of vision impairment (VI) is important for achieving the Sustainable Development Goals. AIM: To estimate the prevalent societal economic impact of presenting VI in Trinidad and Tobago using bottom-up cost and utilisation data from the 2014 National Eye Survey of Trinidad and Tobago. METHODS: We took a societal perspective to combine comprehensive, individual-level cost and utilisation data, with population-based prevalence estimates for VI, and additional data from a contemporaneous national eyecare system survey. We included direct (medical and non-medical) and indirect (productivity loss) costs, and intangible losses in total cost estimates, presented in 2014 Trinidad & Tobago (TT) dollars and UK sterling equivalent. We considered but excluded transfer payments and dead weight losses. Sensitivity analyses explored impact on total cost of parameter uncertainty and assumptions. RESULTS: Individual utilisation and cost data were available for 65.5% (n = 2792/4263) and 59.0% (n = 2516/4263) eligible participants aged ≥40 years, respectively. Participant mean age was 58.4(SD 11.8, range 40-103) years, 56.3% were female. We estimated total societal cost of VI in 2014 at UK£365,650,241 (TT$3,842,324,655), equivalent to £675 per capita (population ≥40 years). Loss of wellbeing accounted for 73.3%. Excluding this, the economic cost was UK£97,547,222 (TT$1,025,045,399), of which indirect costs accounted for 70.5%, followed by direct medical costs (17.9%), and direct non-medical costs (11.6%). CONCLUSION: This study provides a comprehensive estimate of the economic impact of vision loss in a Caribbean country, and highlights the extent to which affected individuals and their families bear the societal economic cost of vision impairment.

Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells.

Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, the leading cause of blindness in older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase (LIPA) and acid sphingomyelinase (SMPD1). In a liver-specific Hepc (Hamp) knockout murine model of systemic iron overload, RPE cells accumulated lipid peroxidation adducts and lysosomes, developed progressive hypertrophy and underwent cell death. Proteomic and lipidomic analyses revealed accumulation of lysosomal proteins, ceramide biosynthetic enzymes and ceramides. The proteolytic enzyme cathepsin D (CTSD) had impaired maturation. A large proportion of lysosomes were galectin-3 (Lgals3) positive, suggesting cytotoxic lysosomal membrane permeabilization. Collectively, these results demonstrate that iron overload induces lysosomal accumulation and impairs lysosomal function, likely due to iron-induced lipid peroxides that can inhibit lysosomal enzymes.

Daily gabapentin improved behavior modification progress and decreased stress in shelter cats from hoarding environments in a double-blind randomized placebo-controlled clinical trial.

OBJECTIVE: To evaluate the impact of daily gabapentin on behavior modification progression and signs of stress in fearful shelter cats from hoarding environments. ANIMALS: 37 cats (32 met inclusion criteria). PROCEDURES: Healthy fearful cats were entered into group (1) gabapentin or (2) placebo upon intake. Both groups received daily behavior modification. Cats received 10 mg/kg of liquid gabapentin or placebo every 12 hours. Daily measures of cat stress score, latency to emerge from hiding, general in-shelter behavior, and urine suppression were collected. Results were analyzed on an intention-to-treat and per-protocol basis (including only cats that received > 75% of their doses). Post-adoption surveys assessed cat social behavior. RESULTS: Of 32 fearful cats, 28 (87.5%) graduated from the behavior modification program in a median of 11 days (range, 4 to 51 days). Per-protocol analysis showed that gabapentin predicted quicker behavior modification progression and lower cat stress score, latency to emerge, and urine suppression compared to placebo. Median time to graduation was reduced by half with gabapentin. Intention-to-treat analysis showed that gabapentin predicted a lower cat stress score and latency to emerge. No differences were observed between groups for general in-shelter behavior. Among limited survey respondents (n = 7), despite showing unsocial behavior in the first week and among unfamiliar people, cats showed social behavior 1 year post-adoption. CLINICAL RELEVANCE: Daily gabapentin was beneficial in behavior modification progress and reduced signs of stress in shelter cats. Fearful cats from hoarding environments can be successfully treated with behavior modification ± daily gabapentin within an animal shelter.

The effects of COVID-19 related shutdowns on perceived lifestyle and prevalence of musculoskeletal discomfort.

BACKGROUND: COVID-19 caused a transition to work-from-home conditions, closures of recreation facilities and cancelation of social events. OBJECTIVE: This study sought to characterize and quantify the impact COVID-19 related shutdowns had on perceptions of health and wellbeing, musculoskeletal discomfort, and physical characteristics of workstation set-up in full time workers who transitioned to working from home. METHODS: 297 participants from 8 countries completed a retrospective pre/post survey design that assessed outcomes prior to COVID-19 shutdowns and when each participant was experiencing peak pandemic-related restrictions. There were 3 categories including, health and wellbeing, musculoskeletal discomfort, and workplace ergonomics. RESULTS: General discomfort on a scale from 1 to 100 increased from 31.4 pre to 39.9 during COVID-19. Notable areas increasing in severity of discomfort from pre to during included the neck (41.8 to 47.7), upper back (36.3 to 41.3) and right wrist (38.7 to 43.5). The percentage of the population experiencing discomfort increased from pre to during in the low back (41.5% to 55.2%), upper back (28.7% to 40.9%), neck (45.5% to 60.9%) and right wrist (16.1% to 23.7%). CONCLUSION: There were three distinct groups for physical activity one group including, one maintaining and one that decreased, which did not have an impact on perceived general discomfort. There was a significant decrease in usage of a desk and adjustable chair and an increase in laptop use. Working from home in some capacity will likely be a more common occurrence which will require further ergonomic assessments and considerations to keep a healthy workforce.

Plant Species' Capacity for Range Shifts at the Habitat and Geographic Scales: A Trade-Off-Based Framework.

Climate change is causing rapid shifts in the abiotic and biotic environmental conditions experienced by plant populations, but we lack generalizable frameworks for predicting the consequences for species. These changes may cause individuals to become poorly matched to their environments, potentially inducing shifts in the distributions of populations and altering species' habitat and geographic ranges. We present a trade-off-based framework for understanding and predicting whether plant species may undergo range shifts, based on ecological strategies defined by functional trait variation. We define a species' capacity for undergoing range shifts as the product of its colonization ability and the ability to express a phenotype well-suited to the environment across life stages (phenotype-environment matching), which are both strongly influenced by a species' ecological strategy and unavoidable trade-offs in function. While numerous strategies may be successful in an environment, severe phenotype-environment mismatches result in habitat filtering: propagules reach a site but cannot establish there. Operating within individuals and populations, these processes will affect species' habitat ranges at small scales, and aggregated across populations, will determine whether species track climatic changes and undergo geographic range shifts. This trade-off-based framework can provide a conceptual basis for species distribution models that are generalizable across plant species, aiding in the prediction of shifts in plant species' ranges in response to climate change.

Consumer attitudes toward bacteriophage applications to pet food.

This study used a two-part questionnaire to investigate consumer knowledge and attitudes toward bacteriophage applications in pet food, pet food safety, and environmental sustainability. Part 1 included questions about pet food safety, sustainability, and knowledge and attitudes toward bacteriophages. Next, participants reviewed educational materials about each, and Part 2 assessed if this increased knowledge of, or changed attitudes toward, bacteriophage application. Participants (n = 80), were recruited through Amazon Mechanical Turk (MT) (n = 45) and Social Media (SM) (n = 35). Mean responses in Part 1 and Part 2 were compared by paired t-tests, and mean responses between MT and SM were compared by t-tests. Participants reported pet food safety was important to them (combined proportion strongly agree or agree, mean ± SD) (75/80, 94%, MT 4.66 ± 0.60, SM 4.71 ± 0.95) and were most concerned with raw pet food safety (51/80, 64%, MT 3.88 ± 0.80, SM 3.17 ± 1.40). Participants rated environmental sustainability as important (61/80, 76%, MT 3.86 ± 0.94, SM 3.97 ± 0.66); however, it was not a strong driver of pet food purchasing (26/80, 33%, MT 3.31 ± 1.25, SM 2.82 ± 0.82). Overall, data showed an increase in knowledge of bacteriophages following a review of educational material. However, in the SM group, no statistically significant difference was observed in the comfort eating food with bacteriophage additives (SM Part 1 3.37 ± 1.05, SM Part 2 3.48 ± 1.12, p = 0.279), whereas the MT group did show an increase (MT Part 1 3.57 ± 1.01, MT Part 2 4.08 ± 0.92, p < 0.001). In the SM group, no statistically significant difference was observed in comfort feeding their pet food with bacteriophage additives (SM Part 1 3.40 ± 1.03, SM Part 2 3.45 ± 1.14, p = 0.571), whereas the MT group did show an increase (MT Part 1 3.57 ± 0.98, MT Part 2 4.31 ± 0.84, p < 0.001). The strongest objections related to safety concerns (20/53, 38%, MT 2.83 ± 0.96, SM 3.27 ± 0.84). These results demonstrate that despite increasing knowledge, there is still hesitancy among some consumers toward bacteriophage applications in pet food.

Quantitative Evaluation of Tactile Foraging Behavior in Pekin and Muscovy Ducks.

Ducks have developed a variety of foraging strategies that utilize touch sensitive bills to match their ecological niche within wetlands. These techniques include diving, sieving, dabbling, and grazing. Ducks exhibiting tactile specialization in foraging outperform visual and non-tactile foraging ducks in behavioral experiments and have a higher percentage of light-touch mechanoreceptor neurons expressing Piezo2 in the trigeminal ganglia. Belonging to two different tribes of Anseriformes, the well-studied tactile specialist Pekin (Tribe Anatini: Anas platyrhynchos domestica) and lesser studied Muscovy (Tribe Cairinini: Cairina moschata domestica) ducks were tested on a series of experiments to assess these birds' functional tactile acuity. Both species of duck were able to separate out and consume edible items from increasing amounts of inedible plastiline clay distractors. They could also both be trained to associate a food reward with plastiline stimuli of differing size and shape using touch alone. However, only females of each species could learn to associate food reward with otherwise identical stimuli differing only in hardness. Pekin females performed significantly better than Muscovy females suggesting the anatomical specializations present in many Anatini may contribute to this type of tactile acuity. These findings have potential relevance in understanding the evolution of tactile ability and feeding ecology.

Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis.

Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.

Reasons for Guardian-Relinquishment of Dogs to Shelters: Animal and Regional Predictors in British Columbia, Canada.

Dogs are relinquished to animal shelters for animal-related or guardian-related reasons. Understanding what drives relinquishment patterns is essential for informing intervention opportunities to keep animals with their guardians. Whereas, overall reasons for relinquishment in a given shelter system have been well explored, analysis of human and animal predictors of relinquishing for a specific reason has not been previously attempted. We used characteristics of relinquishment including year, population of the relinquishing guardian's region, health status of the dog, breed, age group, weight, and sex to predict reasons for dog relinquishment to British Columbia (BC) Society for the Prevention of Cruelty to Animals (SPCA) shelters across BC between 2008 and 2019 (n = 32,081). Relinquishment trends for puppies and adult dogs were also viewed and described. From 2008-2019, the proportion of dogs relinquished relative to total intake remained consistent (range: 31-35%). Primary reasons reported by guardians were having too many dogs (19%), housing issues (17%), personal issues (15%), financial issues (10%), dog behavior (10%), and guardian health (8%). Over years, an increasing proportion of dogs were relinquished for the reason "too many" (OR = 1.16, 95% CI, 1.10-1.23, p < 0.001) and "behavior" (OR = 1.34, 95% CI, 1.26-1.43, p < 0.001), while a decreasing proportion were relinquished due to financial problems (OR = 0.94, 95% CI, 0.88-1.00, p = 0.047). Being a puppy, mixed breed, small, and from a small or medium population center predicted the reason "too many." Being a senior, Healthy, or from a medium or large population center predicted the reason "housing issues." Being a non-puppy, Healthy dog in a large population center predicted the reason "personal issues." Being a puppy, non-Healthy, female, and from a large population center predicted the reason "financial issues." Being a larger young adult or adult and Healthy predicted the reason "dog behavior." Being an adult or senior small dog from a small population center predicted the reason "guardian health." Particularly promising region-specific intervention opportunities include efforts to prevent too many animals in small population centers, improvement of pet-inclusive housing in large population centers, and providing animal care support in large population centers. Accessible veterinary services, including low-cost or subsidized care, likely benefit dog retention across BC.

Transtemporal Sigmoid Sinus Decompression: A Novel Surgical Procedure for the Treatment of Idiopathic Pulsatile Tinnitus.

OBJECTIVE: Idiopathic pulsatile tinnitus (IPT) is associated with high patient morbidity although treatment methods remain unsatisfactory. In the present study, the transtemporal sigmoid sinus decompression is used in the treatment of idiopathic pulsatile tinnitus. STUDY DESIGN: Retrospective case study. SETTING: Tertiary referral center. PATIENTS: From 2005 to 2020, 287 patients presented with a complaint of pulsatile tinnitus. After exclusion criteria, 25 patients were diagnosed with IPT. Those patients underwent treatment and were included in a retrospective study. INTERVENTIONS: Following failed conservative therapies, the primary author performed a transtemporal sigmoid sinus decompression surgery on the patients under general anesthesia. MAIN OUTCOME MEASURES: Long-term resolution of IPT was measured using the Tinnitus Handicap Inventory (THI). Outcome measurements were taken preoperatively, immediately postoperatively, three months postoperatively, and the status of all 25 patients is known at the time of this study. RESULTS: Transtemporal sigmoid sinus decompression was performed on 25 patients (mean age: 51.7 years, 80.0% female). Out of the 25 patients, 23 (92.0%) patients experienced complete resolution of their IPT. Statistically significant differences based on preoperative THI (mean THI: 4.19) were evident immediately after surgery (mean THI: 1.31; p < 0.001), at 3 months postoperatively (mean THI: 1.19; p < 0.001), and over a mean follow-up time of 68.7 months (range, 3-168 months) (mean THI: 1.38; p < 0.001). Out of the two patients considered unsuccessful, Case 21 experienced a partial resolution. No major postoperative complications occurred. CONCLUSIONS: Transtemporal sigmoid sinus decompression is a safe and effective surgical procedure demonstrated to give near total resolution in properly selected patients and provides long-term relief for patients with IPT.

National audit of seven-day working care in radiology.

OBJECTIVES: To evaluate the extent to which our current provision of diagnostic and interventional radiology services matches existing clinical demand and future government proposals as set out in the Royal College of Radiologists published guidance on providing seven-day acute care. METHODS: In June 2018, all UK radiology department audit leads were sent a questionnaire designed to assess compliance for each standard of the Royal College of Radiologists published guidance on providing seven-day acute care. RESULTS: 135 hospitals (68%) responded. Of those that responded, 96% of departments have a diagnostic radiologist rota for clinicians to discuss acute cases and review imaging and 48% of departments do not have a fully staffed consultant rota 24 h a day, seven days a week for interventional radiology. There is significant variance in MRI radiographer availability within departments, ranging from 18.8% during Saturday/Sunday evening/overnight up to a maximum of 63.9% during Saturday daytime. 11% of departments participate in a regional out of hours cross-organisation reporting rota. 40% of departments have no 24/7 RIS technical support and 34% have no PACS technical support out of hours. CONCLUSION: There is a wide variation in practice across radiology departments in the UK. Although there are some standards that the majority of hospitals are achieving, there is a significant short-fall in fundamental aspects of providing acute seven-day care. The multifactorial nature in which these problems have arisen means there is no easy solution to combat these issues. There is a requirement for significant investment and political commitment to improve staffing and infrastructure in order to address the current situation. ADVANCES IN KNOWLEDGE: A UK wide evaluation of the current provision of seven-day working in radiology showing 54% of hospitals do not have a UK working-time regulations compliant Interventional radiology rota, severe lack of availability of acute MRI out of hours and significant deficiencies in providing technical support out of hours. A sustainable and efficient seven-day service is currently not being provided.

Climate Change and Companion Animals: Identifying Links and Opportunities for Mitigation and Adaptation Strategies.

Recent natural disasters and weather extremes are a stark reminder that we live in a climate crisis. Climate scientists and policymakers have asked each discipline to anticipate and create mitigation and adaptation plans in preparation for a worsening future. Companion animals both impact and are impacted by the changing climate through their intrinsically linked relationships to human society. In this theoretical paper, we argue that companion animal scientists are well-suited to address climate change issues. We identify several anticipated climate change outcomes, such as an increase in extreme weather events, human migration, disasters, and an increase in human inequity, and connect these outcomes to identified or hypothesized impacts on companion animals and the human-animal bond. We suggest opportunities to reduce climate change impacts on companion animals that include alterations to owner caretaking behaviors and breeding practices, and education of owners and governments on zoonosis and disaster preparedness. Furthermore, building climate resilience through decreasing inequity in companion animal fields is paramount; and we propose that a starting place can be in animal sheltering and other support services. We also summarize how companion animals and owners' caretaking behaviors are impacting climate change through the use of finite natural resources as well as pollution and carbon emissions. We propose that replacement, reduction, and refinement, that guide laboratory animal research, can also be useful to mitigate the effects of companion animals on the environment. We suggest criteria for successful mitigation and adaptation plans to include equitability, sustainability, respect for animals, and measurability. Finally, we end on a call to all companion animal professionals to actively consider their role in mitigating the impact of companion animals on the climate and preparing for the fallout of climate change in their communities.

A postbiotic from Aspergillus oryzae attenuates the impact of heat stress in ectothermic and endothermic organisms.

Heat stress is detrimental to food-producing animals and animal productivity remains suboptimal despite the use of heat abatement strategies during summer. Global warming and the increase of frequency and intensity of heatwaves are likely to continue and, thus, exacerbate the problem of heat stress. Heat stress leads to the impairment of physiological and cellular functions of ectothermic and endothermic animals. Therefore, it is critical to conceive ways of protecting animals against the pathological effects of heat stress. In experiments with endothermic animals highly sensitive to heat (Bos taurus), we have previously reported that heat-induced systemic inflammation can be ameliorated in part by nutritional interventions. The experiments conducted in this report described molecular and physiological adaptations to heat stress using Drosophila melanogaster and dairy cow models. In this report, we expand previous work by first demonstrating that the addition of a postbiotic from Aspergillus oryzae (AO) into the culture medium of ectothermic animals (Drosophila melanogaster) improved survival to heat stress from 30 to 58%. This response was associated with downregulation of genes involved in the modulation of oxidative stress and immunity, most notably metallothionein B, C, and D. In line with these results, we subsequently showed that the supplementation with the AO postbiotic to lactating dairy cows experiencing heat stress decreased plasma concentrations of serum amyloid A and lipopolysaccharide-binding protein, and the expression of interleukin-6 in white blood cells. These alterations were paralleled by increased synthesis of energy-corrected milk and milk components, suggesting enhanced nutrient partitioning to lactogenesis and increased metabolic efficiency. In summary, this work provides evidence that a postbiotic from AO enhances thermal tolerance likely through a mechanism that entails reduced inflammation.

The Impact of Nonpharmacological Interventions on Patient Experience, Opioid Use, and Health Care Utilization in Adult Cardiac Surgery Patients: Protocol for a Mixed Methods Study.

BACKGROUND: Despite pharmacological treatments, patients undergoing cardiac surgery experience severe anxiety and pain, which adversely affect outcomes. Previous work examining pediatric and nonsurgical adult patients has documented the effectiveness of inexpensive, nonpharmacological techniques to reduce anxiety and pain as well as health care costs and length of hospitalization. However, the impact of nonpharmacological interventions administered by a dedicated comfort coach has not been evaluated in an adult surgical setting. OBJECTIVE: This trial aims to assess whether nonpharmacological interventions administered by a trained comfort coach affect patient experience, opioid use, and health care utilization compared with usual care in adult cardiac surgery patients. This study has 3 specific aims: assess the effect of a comfort coach on patient experience, measure differences in inpatient and outpatient opioid use and postoperative health care utilization, and qualitatively evaluate the comfort coach intervention. METHODS: To address these aims, we will perform a prospective, randomized controlled trial of 154 adult cardiac surgery patients at Michigan Medicine. Opioid-naive patients undergoing first-time, elective cardiac surgery via sternotomy will be randomized to undergo targeted interventions from a comfort coach (intervention) versus usual care (control). The individualized comfort coach interventions will be administered at 6 points: preoperative outpatient clinic, preoperative care unit on the day of surgery, extubation, chest tube removal, hospital discharge, and 30-day clinic follow-up. To address aim 1, we will examine the effect of a comfort coach on perioperative anxiety, self-reported pain, functional status, and patient satisfaction through validated surveys administered at preoperative outpatient clinic, discharge, 30-day follow-up, and 90-day follow-up. For aim 2, we will record inpatient opioid use and collect postdischarge opioid use and pain-related outcomes through an 11-item questionnaire administered at the 30-day follow-up. Hospital length of stay, readmission, number of days in an extended care facility, emergency room, urgent care, and an unplanned doctor's office visit will be recorded as the primary composite endpoint defined as total days spent at home within the first 30 days after surgery. For aim 3, we will perform semistructured interviews with patients in the intervention arm to understand the comfort coach intervention through a thematic analysis. RESULTS: This trial, funded by Blue Cross Blue Shield of Michigan Foundation in 2019, is presently enrolling patients with anticipated manuscript submissions from our primary aims targeted for the end of 2020. CONCLUSIONS: Data generated from this mixed methods study will highlight effective nonpharmacological techniques and support a multidisciplinary approach to perioperative care during the adult cardiac surgery patient experience. This study's findings may serve as the foundation for a subsequent multicenter trial and broader dissemination of these techniques to other types of surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04051021; https://clinicaltrials.gov/ct2/show/NCT04051021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21350.